Showing papers by "Laval University published in 2008"

Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)

Abstract: Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation of the membranes lining the nose. It is a global health problem that causes major illness and disability worldwide. Over 600 million patients from all countries, all ethnic groups and of all ages suffer from allergic rhinitis. It affects social life, sleep, school and work and its economic impact is substantial. Risk factors for allergic rhinitis are well identified. Indoor and outdoor allergens as well as occupational agents cause rhinitis and other allergic diseases. The role of indoor and outdoor pollution is probably very important, but has yet to be fully understood both for the occurrence of the disease and its manifestations. In 1999, during the Allergic Rhinitis and its Impact on Asthma (ARIA) WHO workshop, the expert panel proposed a new classification for allergic rhinitis which was subdivided into 'intermittent' or 'persistent' disease. This classification is now validated. The diagnosis of allergic rhinitis is often quite easy, but in some cases it may cause problems and many patients are still under-diagnosed, often because they do not perceive the symptoms of rhinitis as a disease impairing their social life, school and work. The management of allergic rhinitis is well established and the ARIA expert panel based its recommendations on evidence using an extensive review of the literature available up to December 1999. The statements of evidence for the development of these guidelines followed WHO rules and were based on those of Shekelle et al. A large number of papers have been published since 2000 and are extensively reviewed in the 2008 Update using the same evidence-based system. Recommendations for the management of allergic rhinitis are similar in both the ARIA workshop report and the 2008 Update. In the future, the GRADE approach will be used, but is not yet available. Another important aspect of the ARIA guidelines was to consider co-morbidities. Both allergic rhinitis and asthma are systemic inflammatory conditions and often co-exist in the same patients. In the 2008 Update, these links have been confirmed. The ARIA document is not intended to be a standard-of-care document for individual countries. It is provided as a basis for physicians, health care professionals and organizations involved in the treatment of allergic rhinitis and asthma in various countries to facilitate the development of relevant local standard-of-care documents for patients.

Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events

Abstract: Background In patients who have vascular disease or high-risk diabetes without heart failure, angiotensin-converting–enzyme (ACE) inhibitors reduce mortality and morbidity from cardiovascular causes, but the role of angiotensin-receptor blockers (ARBs) in such patients is unknown. We compared the ACE inhibitor ramipril, the ARB telmisartan, and the combination of the two drugs in patients with vascular disease or high-risk diabetes. Methods After a 3-week, single-blind run-in period, patients underwent double-blind randomization, with 8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive 80 mg of telmisartan per day, and 8502 assigned to receive both drugs (combination therapy). The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure. Results Mean blood pressure was lower in both the telmisartan group (a 0.9/0.6 mm Hg greater reduction) and the combination-therapy group (a 2.4/1.4 mm Hg greater reduction) than in the ramipril group. At a median follow-up of 56 months, the primary outcome had occurred in 1412 patients in the ramipril group (16.5%), as compared with 1423 patients in the telmisartan group (16.7%; relative risk, 1.01; 95% confidence interval [CI], 0.94 to 1.09). As compared with the ramipril group, the telmisartan group had lower rates of cough (1.1% vs. 4.2%, P<0.001) and angioedema (0.1% vs. 0.3%, P = 0.01) and a higher rate of hypotensive symptoms (2.6% vs. 1.7%, P<0.001); the rate of syncope was the same in the two groups (0.2%). In the combination-therapy group, the primary outcome occurred in 1386 patients (16.3%; relative risk, 0.99; 95% CI, 0.92 to 1.07); as compared with the ramipril group, there was an increased risk of hypotensive symptoms (4.8% vs. 1.7%, P<0.001), syncope (0.3% vs. 0.2%, P = 0.03), and renal dysfunction (13.5% vs. 10.2%, P<0.001). Conclusions Telmisartan was equivalent to ramipril in patients with vascular disease or highrisk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit. (ClinicalTrials.gov number, NCT00153101.)

Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes

Abstract: Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms Recent reviews have described the range of assays that have been used for this purpose(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi) Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response

TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis

Abstract: Recently, TDP-43 was identified as a key component of ubiquitinated aggregates in amyotrophic lateral sclerosis (ALS), an adult-onset neurological disorder that leads to the degeneration of motor neurons. Here we report eight missense mutations in nine individuals--six from individuals with sporadic ALS (SALS) and three from those with familial ALS (FALS)--and a concurring increase of a smaller TDP-43 product. These findings further corroborate that TDP-43 is involved in ALS pathogenesis.

Argonaute proteins: key players in RNA silencing

Abstract: During the past decade, small non-coding RNAs have rapidly emerged as important contributors to gene regulation. To carry out their biological functions, these small RNAs require a unique class of proteins called Argonautes. The discovery and our comprehension of this highly conserved protein family is closely linked to the study of RNA-based gene silencing mechanisms. With their functional domains, Argonaute proteins can bind small non-coding RNAs and control protein synthesis, affect messenger RNA stability and even participate in the production of a new class of small RNAs, Piwi-interacting RNAs.

Phage response to CRISPR-encoded resistance in Streptococcus thermophilus.

Abstract: Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated genes are linked to a mechanism of acquired resistance against bacteriophages Bacteria can integrate short stretches of phage-derived sequences (spacers) within CRISPR loci to become phage resistant In this study, we further characterized the efficiency of CRISPR1 as a phage resistance mechanism in Streptococcus thermophilus First, we show that CRISPR1 is distinct from previously known phage defense systems and is effective against the two main groups of S thermophilus phages Analyses of 30 bacteriophage-insensitive mutants of S thermophilus indicate that the addition of one new spacer in CRISPR1 is the most frequent outcome of a phage challenge and that the iterative addition of spacers increases the overall phage resistance of the host The added new spacers have a size of between 29 to 31 nucleotides, with 30 being by far the most frequent Comparative analysis of 39 newly acquired spacers with the complete genomic sequences of the wild-type phages 2972, 858, and DT1 demonstrated that the newly added spacer must be identical to a region (named proto-spacer) in the phage genome to confer a phage resistance phenotype Moreover, we found a CRISPR1-specific sequence (NNAGAAW) located downstream of the proto-spacer region that is important for the phage resistance phenotype Finally, we show through the analyses of 20 mutant phages that virulent phages are rapidly evolving through single nucleotide mutations as well as deletions, in response to CRISPR1

Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia

Abstract: The primary outcome, the mean (±SE) change in the carotid-artery intima–media thickness, was 0.0058±0.0037 mm in the simvastatin-only group and 0.0111±0.0038 mm in the simvastatin-plus-ezetimibe (combined-therapy) group (P = 0.29). Secondary outcomes (consisting of other variables regarding the intima–media thickness of the carotid and femoral arteries) did not differ significantly between the two groups. At the end of the study, the mean (±SD) LDL cholesterol level was 192.7±60.3 mg per deciliter (4.98±1.56 mmol per liter) in the simvastatin group and 141.3±52.6 mg per deciliter (3.65±1.36 mmol per liter) in the combined-therapy group (a between-group difference of 16.5%, P<0.01). The differences between the two groups in reductions in levels of triglycerides and C-reactive protein were 6.6% and 25.7%, respectively, with greater reductions in the combined-therapy group (P<0.01 for both comparisons). Side-effect and safety profiles were similar in the two groups. Conclusions In patients with familial hypercholesterolemia, combined therapy with ezetimibe and simvastatin did not result in a significant difference in changes in intima–media thickness, as compared with simvastatin alone, despite decreases in levels of LDL cholesterol and C-reactive protein. (ClinicalTrials.gov number, NCT00552097.)

Net carbon dioxide losses of northern ecosystems in response to autumn warming

Abstract: The carbon balance of terrestrial ecosystems is particularly sensitive to climatic changes in autumn and spring(1-4), with spring and autumn temperatures over northern latitudes having risen by about 1.1 degrees C and 0.8 degrees C, respectively, over the past two decades(5). A simultaneous greening trend has also been observed, characterized by a longer growing season and greater photosynthetic activity(6,7). These observations have led to speculation that spring and autumn warming could enhance carbon sequestration and extend the period of net carbon uptake in the future(8). Here we analyse interannual variations in atmospheric carbon dioxide concentration data and ecosystem carbon dioxide fluxes. We find that atmospheric records from the past 20 years show a trend towards an earlier autumn- to- winter carbon dioxide build- up, suggesting a shorter net carbon uptake period. This trend cannot be explained by changes in atmospheric transport alone and, together with the ecosystem flux data, suggest increasing carbon losses in autumn. We use a process- based terrestrial biosphere model and satellite vegetation greenness index observations to investigate further the observed seasonal response of northern ecosystems to autumnal warming. We find that both photosynthesis and respiration increase during autumn warming, but the increase in respiration is greater. In contrast, warming increases photosynthesis more than respiration in spring. Our simulations and observations indicate that northern terrestrial ecosystems may currently lose carbon dioxide in response to autumn warming, with a sensitivity of about 0.2 PgC degrees C-1, offsetting 90% of the increased carbon dioxide uptake during spring. If future autumn warming occurs at a faster rate than in spring, the ability of northern ecosystems to sequester carbon may be diminished earlier than previously suggested(9,10).

Healthcare professionals' intentions and behaviours: A systematic review of studies based on social cognitive theories

Abstract: There is an important gap between the implications of clinical research evidence and the routine clinical practice of healthcare professionals. Because individual decisions are often central to adoption of a clinical-related behaviour, more information about the cognitive mechanisms underlying behaviours is needed to improve behaviour change interventions targeting healthcare professionals. The aim of this study was to systematically review the published scientific literature about factors influencing health professionals' behaviours based on social cognitive theories. These theories refer to theories where individual cognitions/thoughts are viewed as processes intervening between observable stimuli and responses in real world situations. We searched psycINFO, MEDLINE, EMBASE, CIHNAL, Index to theses, PROQUEST dissertations and theses and Current Contents for articles published in English only. We included studies that aimed to predict healthcare professionals' intentions and behaviours with a clear specification of relying on a social cognitive theory. Information on percent of explained variance (R2) was used to compute the overall frequency-weighted mean R2 to evaluate the efficacy of prediction in several contexts and according to different methodological aspects. The cognitive factors most consistently associated with prediction of healthcare professionals' intention and behaviours were documented. Seventy eight studies met the inclusion criteria. Among these studies, 72 provided information on the determinants of intention and 16 prospective studies provided information on the determinants of behaviour. The theory most often used as reference was the Theory of Reasoned Action (TRA) or its extension the Theory of Planned Behaviour (TPB). An overall frequency-weighted mean R2 of 0.31 was observed for the prediction of behaviour; 0.59 for the prediction of intention. A number of moderators influenced the efficacy of prediction; frequency-weighted mean R2 varied from 0.001 to 0.58 for behaviour and 0.19 to 0.81 for intention. Our results suggest that the TPB appears to be an appropriate theory to predict behaviour whereas other theories better capture the dynamic underlying intention. In addition, given the variations in efficacy of prediction, special care should be given to methodological issues, especially to better define the context of behaviour performance.

Diversity, Activity, and Evolution of CRISPR Loci in Streptococcus thermophilus

Abstract: Clustered regularly interspaced short palindromic repeats (CRISPR) are hypervariable loci widely distributed in prokaryotes that provide acquired immunity against foreign genetic elements. Here, we characterize a novel Streptococcus thermophilus locus, CRISPR3, and experimentally demonstrate its ability to integrate novel spacers in response to bacteriophage. Also, we analyze CRISPR diversity and activity across three distinct CRISPR loci in several S. thermophilus strains. We show that both CRISPR repeats and cas genes are locus specific and functionally coupled. A total of 124 strains were studied, and 109 unique spacer arrangements were observed across the three CRISPR loci. Overall, 3,626 spacers were analyzed, including 2,829 for CRISPR1 (782 unique), 173 for CRISPR2 (16 unique), and 624 for CRISPR3 (154 unique). Sequence analysis of the spacers revealed homology and identity to phage sequences (77%), plasmid sequences (16%), and S. thermophilus chromosomal sequences (7%). Polymorphisms were observed for the CRISPR repeats, CRISPR spacers, cas genes, CRISPR motif, locus architecture, and specific sequence content. Interestingly, CRISPR loci evolved both via polarized addition of novel spacers after exposure to foreign genetic elements and via internal deletion of spacers. We hypothesize that the level of diversity is correlated with relative CRISPR activity and propose that the activity is highest for CRISPR1, followed by CRISPR3, while CRISPR2 may be degenerate. Globally, the dynamic nature of CRISPR loci might prove valuable for typing and comparative analyses of strains and microbial populations. Also, CRISPRs provide critical insights into the relationships between prokaryotes and their environments, notably the coevolution of host and viral genomes.

Epigenomic Profiling Reveals DNA-Methylation Changes Associated with Major Psychosis

Abstract: Epigenetic misregulation is consistent with various non-Mendelian features of schizophrenia and bipolar disorder. To date, however, few studies have investigated the role of DNA methylation in major psychosis, and none have taken a genome-wide epigenomic approach. In this study we used CpG-island microarrays to identify DNA-methylation changes in the frontal cortex and germline associated with schizophrenia and bipolar disorder. In the frontal cortex we find evidence for psychosis-associated DNA-methylation differences in numerous loci, including several involved in glutamatergic and GABAergic neurotransmission, brain development, and other processes functionally linked to disease etiology. DNA-methylation changes in a significant proportion of these loci correspond to reported changes of steady-state mRNA level associated with psychosis. Gene-ontology analysis highlighted epigenetic disruption to loci involved in mitochondrial function, brain development, and stress response. Methylome network analysis uncovered decreased epigenetic modularity in both the brain and the germline of affected individuals, suggesting that systemic epigenetic dysfunction may be associated with major psychosis. We also report evidence for a strong correlation between DNA methylation in the MEK1 gene promoter region and lifetime antipsychotic use in schizophrenia patients. Finally, we observe that frontal-cortex DNA methylation in the BDNF gene is correlated with genotype at a nearby nonsynonymous SNP that has been previously associated with major psychosis. Our data are consistent with the epigenetic theory of major psychosis and suggest that DNA-methylation changes are important to the etiology of schizophrenia and bipolar disorder.

Identifying Canadian Freshwater Fishes through DNA Barcodes

Abstract: Background DNA barcoding aims to provide an efficient method for species-level identifications using an array of species specific molecular tags derived from the 5′ region of the mitochondrial cytochrome c oxidase I (COI) gene. The efficiency of the method hinges on the degree of sequence divergence among species and species-level identifications are relatively straightforward when the average genetic distance among individuals within a species does not exceed the average genetic distance between sister species. Fishes constitute a highly diverse group of vertebrates that exhibit deep phenotypic changes during development. In this context, the identification of fish species is challenging and DNA barcoding provide new perspectives in ecology and systematics of fishes. Here we examined the degree to which DNA barcoding discriminate freshwater fish species from the well-known Canadian fauna, which currently encompasses nearly 200 species, some which are of high economic value like salmons and sturgeons.

A consensus approach toward the standardization of back pain definitions for use in prevalence studies

Abstract: A modified Delphi study conducted with 28 experts in back pain research from 12 countries. OBJECTIVE. To identify standardized definitions of low back pain that could be consistently used by investigators in prevalence studies to provide comparable data. SUMMARY OF BACKGROUND DATA. Differences in the definition of back pain prevalence in population studies lead to heterogeneity in study findings, and limitations or impossibilities in comparing or summarizing prevalence figures from different studies. METHODS. Back pain definitions were identified from 51 articles reporting population-based prevalence studies, and dissected into 77 items documenting 7 elements. These items were submitted to a panel of experts for rating and reduction, in 3 rounds (participation: 76%). Preliminary results were presented and discussed during the Amsterdam Forum VIII for Primary Care Research on Low Back Pain, compared with scientific evidence and confirmed and fine-tuned by the panel in a fourth round and the preparation of the current article. RESULTS. Two definitions were agreed on a minimal definition (with 1 question covering site of low back pain, symptoms observed, and time frame of the measure, and a second question on severity of low back pain) and an optimal definition that is made from the minimal definition and add-ons (covering frequency and duration of symptoms, an additional measure of severity, sciatica, and exclusions) that can be adapted to different needs. CONCLUSION. These definitions provide standards that may improve future comparisons of low back pain prevalence figures by person, place and time characteristics, and offer opportunities for statistical summaries.

Online planning algorithms for POMDPs

Abstract: Partially Observable Markov Decision Processes (POMDPs) provide a rich framework for sequential decision-making under uncertainty in stochastic domains. However, solving a POMDP is often intractable except for small problems due to their complexity. Here, we focus on online approaches that alleviate the computational complexity by computing good local policies at each decision step during the execution. Online algorithms generally consist of a lookahead search to find the best action to execute at each time step in an environment. Our objectives here are to survey the various existing online POMDP methods, analyze their properties and discuss their advantages and disadvantages; and to thoroughly evaluate these online approaches in different environments under various metrics (return, error bound reduction, lower bound improvement). Our experimental results indicate that state-of-the-art online heuristic search methods can handle large POMDP domains efficiently.

Fish invasions in the world's river systems: when natural processes are blurred by human activities.

Abstract: Because species invasions are a principal driver of the human-induced biodiversity crisis, the identification of the major determinants of global invasions is a prerequisite for adopting sound conservation policies. Three major hypotheses, which are not necessarily mutually exclusive, have been proposed to explain the establishment of non-native species: the “human activity” hypothesis, which argues that human activities facilitate the establishment of non-native species by disturbing natural landscapes and by increasing propagule pressure; the “biotic resistance” hypothesis, predicting that species-rich communities will readily impede the establishment of non-native species; and the “biotic acceptance” hypothesis, predicting that environmentally suitable habitats for native species are also suitable for non-native species. We tested these hypotheses and report here a global map of fish invasions (i.e., the number of non-native fish species established per river basin) using an original worldwide dataset of freshwater fish occurrences, environmental variables, and human activity indicators for 1,055 river basins covering more than 80% of Earth's surface. First, we identified six major invasion hotspots where non-native species represent more than a quarter of the total number of species. According to the World Conservation Union, these areas are also characterised by the highest proportion of threatened fish species. Second, we show that the human activity indicators account for most of the global variation in non-native species richness, which is highly consistent with the “human activity” hypothesis. In contrast, our results do not provide support for either the “biotic acceptance” or the “biotic resistance” hypothesis. We show that the biogeography of fish invasions matches the geography of human impact at the global scale, which means that natural processes are blurred by human activities in driving fish invasions in the world's river systems. In view of our findings, we fear massive invasions in developing countries with a growing economy as already experienced in developed countries. Anticipating such potential biodiversity threats should therefore be a priority.

Optimal learning in optimal contexts: The role of self-determination in education

Abstract: In English : This literature review provides an overview of education studies that have been guided by self-determination theory (SDT). First, the authors examine studies that have assessed motivation based on SDT. Second, the authors detail research that has focussed on the linkages between motivation types and students' behavioural, affective, and cognitive outcomes. Third, the authors present studies on how learning contexts (parents, teachers) contribute to students' motivational resources. The authors conclude that the motivation types proposed by SDT are important for understanding how students thrive and succeed at school. The authors also highlight the significant role played by teachers and parents in the development of student motivation. The authors conclude with a summary of the benefits of self-motivation for learning and offer some recommendations for the field. (PsycINFO Database Record (c) 2016 APA, all rights reserved) Resume en francais (langue de l'article en anglais) : Le present article procure une vue d'ensemble des etudes sur l'education qui ont ete guidees par la theorie de l'autodetermination. En premier lieu, nous examinons les etudes qui ont evalue la motivation fondee sur la theorie de l'autodetermination. Nous expliquons ensuite la recherche portant sur les liens existant entre les types de motivation et les resultats des etudiants en matiere de comportement et de composantes affectives et cognitives. Nous presentons aussi les etudes sur les contextes d'apprentissage (parents, enseignants) qui contribuent aux ressources motivationnelles des etudiants. Nous en deduisons que les types de motivation proposes par la theorie de l'autodetermination permettent de comprendre les elements qui permettent aux etudiants de se demarquer et de reussir en milieu scolaire. Nous mettons aussi en relief le role important que jouent les enseignants et les parents dans le developpement de la motivation de l'eudiant. En conclusion, nous presentons un resume des bienfaits de l'automotivation dans le cadre de l'apprentissage et offrons quelques recommandations pertinentes au domaine en question. (PsycINFO Database Record (c) 2016 APA, all rights reserved)

Optical Detection of DNA and Proteins with Cationic Polythiophenes

Abstract: In recent years, intense research has been carried out worldwide with the goal of developing simple, sensitive, and specific detection tools for biomedical applications. Along these lines, we reported in 2002 on cationic polythiophene derivatives able to provide ultrasensitive detection levels and the capability to distinguish perfect matches from oligonucleotides having as little as a single base mismatch. It was shown that the intrinsic fluorescence of the random-coil polymers quenches as a result of the planar, highly conjugated conformation adopted by the polymers when complexed with a single-strand DNA (ssDNA) capture probe but increases again after hybridization with the perfectly matched complementary strand. This change in fluorescence intensity is mainly due to a modification in the delocalization of π electrons along the carbon chain backbone that occurs when switching between the two conformations. Thus, by monitoring, via the change in fluorescence intensity, the hybridization of the complemen...

Poly(2,7-carbazole)s: structure-property relationships.

Abstract: Conjugated polymers combine the interesting optical and electrical properties of metals with the processing advantages and mechanical properties of traditional synthetic polymers. With clever use of a variety of synthetic tools, researchers have prepared highly pure polymers with optimized physical properties during the past 30 years. For example, the synthesis of well-defined polyacetylenes, polyphenylenes, polythiophenes, polyfluorenes, and other conjugated polymers have significantly improved the performance of these polymeric materials. However, one important class of conjugated polymers was missing from this chemical inventory: easy access to well-defined poly(2,7-carbazole)s and related polymers. This Account highlights advances in the synthesis of poly(2,7-carbazole) derivatives since they were first reported in 2001. Starting from 2-nitro-biphenyl derivatives, 2,7-functionalized carbazoles are typically obtained from Cadogan ring-closure reactions. In a second step, Yamamoto, Stille, Suzuki, or Ho...

A new perspective on concepts of asthma severity and control

Abstract: Concepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used interchangeably. This review, arising from the work of an American Thoracic Society/European Respiratory Society Task Force, identifies the need for separate concepts of control and severity, describes their evolution in asthma guidelines and provides a framework for understanding the relationship between current concepts of asthma phenotype, severity and control. "Asthma control" refers to the extent to which the manifestations of asthma have been reduced or removed by treatment. Its assessment should incorporate the dual components of current clinical control (e.g. symptoms, reliever use and lung function) and future risk (e.g. exacerbations and lung function decline). The most clinically useful concept of asthma severity is based on the intensity of treatment required to achieve good asthma control, i.e. severity is assessed during treatment. Severe asthma is defined as the requirement for (not necessarily just prescription or use of) high-intensity treatment. Asthma severity may be influenced by the underlying disease activity and by the patient's phenotype, both of which may be further described using pathological and physiological markers. These markers can also act as surrogate measures for future risk.

Science with ASKAP: The Australian square-kilometre-array pathfinder

Abstract: The future of cm and m-wave astronomy lies with the Square Kilometre Array (SKA), a telescope under development by a consortium of 17 countries. The SKA will be 50 times more sensitive than any existing radio facility. A majority of the key science for the SKA will be addressed through large-area imaging of the Universe at frequencies from 300 MHz to a few GHz. The Australian SKA Pathfinder (ASKAP) is aimed squarely in this frequency range, and achieves instantaneous wide-area imaging through the development and deployment of phase-array feed systems on parabolic reflectors. This large field-of-view makes ASKAP an unprecedented synoptic telescope poised to achieve substantial advances in SKA key science. The central core of ASKAP will be located at the Murchison Radio Observatory in inland Western Australia, one of the most radio-quiet locations on the Earth and one of the sites selected by the international community as a potential location for the SKA. Following an introductory description of ASKAP, this document contains 7 chapters describing specific science programmes for ASKAP. In summary, the goals of these programmes are as follows: The combination of location, technological innovation and scientific program will ensure that ASKAP will be a world-leading radio astronomy facility, closely aligned with the scientific and technical direction of the SKA. A brief summary chapter emphasizes the point, and considers discovery space.