Genome-wide association study to identify genetic determinants of severe asthma.

Background: The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear.

Objective: To identify common genetic variants affecting susceptibility to severe asthma.

Satellite-based estimates of ambient air pollution and global variations in childhood asthma prevalence.

Background: The effect of ambient air pollution on global variations and trends in asthma prevalence is unclear.

Objectives: Our goal was to investigate community-level associations between asthma prevalence data from the International Study of Asthma and Allergies in Childhood (ISAAC) and satellite-based estimates of particulate matter with aerodynamic diameter < 2.5 µm (PM₂.

The challenges of replicating the methodology between Phases I and III of the ISAAC programme.

Background: The International Study of Asthma and Allergies in Childhood (ISAAC) used standardised methods to examine symptom prevalence of asthma, rhinitis and eczema in adolescents and children between Phases I and III. Centres followed essential rules to ensure comparability of methodology, examined by a centralised data centre.

Methods: Centre reports (CRs) were compared for both phases and age groups.

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.

Cochlear implantation in children with complex needs - outcomes.

Objectives: Prospective review of the assessment and outcomes of children with complex needs receiving cochlear implants (CIs) at the Yorkshire Cochlear Implant Service (YCIS).

Methods: Nineteen children with complex needs were assessed pre-implant and 12 months post-implant switch-on using appropriate developmental-related audiology, categories of auditory performance (CAP), meaningful auditory information scale (MAIS), listening progress score (LiP), and meaningful use of speech scale (MUSS). Outcomes were compared with 230 children at the YCIS without complex needs.

ERK2 drives tumour cell migration in three-dimensional microenvironments by suppressing expression of Rab17 and liprin-β2.

Upregulation of the extracellular signal-regulated kinase (ERK) pathway has been shown to contribute to tumour invasion and progression. Because the two predominant ERK isoforms (ERK1 and ERK2, also known as MAPK3 and MAPK1, respectively) are highly homologous and have indistinguishable kinase activities in vitro, both enzymes were believed to be redundant and interchangeable. To challenge this view, we show that ERK2 silencing inhibits invasive migration of MDA-MB-231 cells, and re-expression of ERK2 but not ERK1 restores the normal invasive phenotype.

Time-lapse imaging of the dynamics of CNS glial-axonal interactions in vitro and ex vivo.

Background: Myelination is an exquisite and dynamic example of heterologous cell-cell interaction, which consists of the concentric wrapping of multiple layers of oligodendrocyte membrane around neuronal axons. Understanding the mechanism by which oligodendrocytes ensheath axons may bring us closer to designing strategies to promote remyelination in demyelinating diseases. The main aim of this study was to follow glial-axonal interactions over time both in vitro and ex vivo to visualize the various stages of myelination.

Changes over time in the relationship between symptoms of asthma, rhinoconjunctivitis and eczema: a global perspective from the International Study of Asthma and Allergies in Childhood (ISAAC).

Background: The International Study of Asthma and Allergies in Childhood (ISAAC) identified trends in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema over a seven-year period. We hypothesised that environmental influences on the three diseases are different and therefore investigated the correlation over time between trends in the prevalence of these diseases and their combinations at centre and individual level.

Methods: Centre level analyses were correlations between time trends in the prevalence of symptoms.

Hearing in 44-45 year olds with m.1555A>G, a genetic mutation predisposing to aminoglycoside-induced deafness: a population based cohort study.

Background The mitochondrial DNA mutation m.1555A>G predisposes to permanent idiosyncratic aminoglycoside-induced deafness that is independent of dose. Research suggests that in some families, m.

Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis.

Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies.

Rab25 and CLIC3 collaborate to promote integrin recycling from late endosomes/lysosomes and drive cancer progression.

Here we show that Rab25 permits the sorting of ligand-occupied, active-conformation α5β1 integrin to late endosomes/lysosomes. Photoactivation and biochemical approaches show that lysosomally targeted integrins are not degraded but are retrogradely transported and recycled to the plasma membrane at the back of invading cells. This requires CLIC3, a protein upregulated in Rab25-expressing cells and tumors, which colocalizes with active α5β1 in late endosomes/lysosomes.

Tuberculosis, bacillus Calmette-Guérin vaccination, and allergic disease: findings from the International Study of Asthma and Allergies in Childhood Phase Two.

Some have suggested a protective effect of tuberculosis (TB) infection on allergic disease risk, but few studies have examined the association between the two. We therefore investigated whether TB disease and bacillus Calmette-Guérin (BCG) vaccination in early life protect against allergic disease. Information on allergic disease symptoms, past TB disease, and BCG vaccination as well as potential confounding factors was gathered by parental questionnaire from a randomly selected subset of 23,901 8- to 12-yr-old schoolchildren in 20 centers in both developed and developing countries.

Sex differences in the relationship between inflammatory and hemostatic biomarkers and metabolic syndrome: British 1958 Birth Cohort.

Background: Circulating levels of C-reactive protein (CRP), fibrinogen, fibrin D-dimer, tissue plasminogen activator antigen (t-PA) and von Willebrand factor (VWF) are associated with incident coronary heart disease (CHD). However, their associations with metabolic syndrome and its components in large populations of men and women have not been well defined.

Objectives: We compare the sex associations of these biomarkers with established CHD risk factors, metabolic syndrome and its components in a large cohort.

A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study.

Background: Atopy and plasma IgE concentration are genetically complex traits, and the specific genetic risk factors that lead to IgE dysregulation and clinical atopy are an area of active investigation.

Objective: We sought to ascertain the genetic risk factors that lead to IgE dysregulation.

Methods: A genome-wide association study (GWAS) was performed in 6819 participants from the Framingham Heart Study (FHS).

A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order.

Background: Hay fever or seasonal allergic rhinitis (AR) is a chronic disorder associated with IgE sensitization to grass. The underlying genetic variants have not been studied comprehensively. There is overwhelming evidence that those who have older siblings have less AR, although the mechanism for this remains unclear.

Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.

Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2.

Outcomes with bilateral cochlear implantation following sudden dual sensory loss after ethylene glycol poisoning.

Acute loss of vision accompanied by profound loss of hearing is fortunately rare, but has a catastrophic effect on both the patient and their family. Re-establishing communication and spatial awareness are high priorities. We describe the case of a 45 year-old man who presented as a result of poisoning by ethylene glycol.

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events.

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.

Lack of evidence for a protective effect of prolonged breastfeeding on childhood eczema: lessons from the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two.

Background: Exclusive breastfeeding for at least 4 months is recommended by many governments and allergy organizations to prevent allergic disease.

Objectives: To investigate whether exclusive breastfeeding protects against childhood eczema.

Methods: Study subjects comprised 51,119 randomly selected 8- to 12-year-old schoolchildren in 21 countries.

Genetic risks and childhood-onset asthma.

Recent large-scale genome-wide association studies have successfully identified several genetic loci that influence asthma susceptibility. The loci thus far identified confer a high population attributable risk for childhood-onset disease and have provided a better understanding of the primary mechanisms underlying asthma and a clear focus for new therapies to treat the disease. The loci are of limited utility for diagnostic or predictive genetic testing.

Crystallographically aligned carbon nanotubes grown on few-layer graphene films.

Carbon nanotubes are grown on few-layer graphene films using chemical vapor deposition without a carbon feedstock gas. We find that the nanotubes show a striking alignment to specific crystal orientations of the few-layer graphene films. The nanotubes are oriented predominantly at 60 degree intervals and are offset 30 degrees from crystallographically oriented etch tracks, indicating alignment to the armchair axes of the few-layer graphene films.