Multiplexed microsphere diagnostic tools in gene expression applications: factors and futures

Microarrays have received significant attention in recent years as scientists have firstly identified factors that can produce reduced confidence in gene expression data obtained on these platforms, and secondly sought to establish laboratory practices and a set of standards by which data are reported with integrity. Microsphere-based assays represent a new generation of diagnostics in this field capable of providing substantial quantitative and qualitative information from gene expression profiling. However, for gene expression profiling, this type of platform is still in the demonstration phase, with issues arising from comparative studies in the literature not yet identified. It is desirable to identify potential parameters that are established as important in controlling the information derived from microsphere-based hybridizations to quantify gene expression. As these evolve, a standard set of parameters will be established that are required to be provided when data are submitted for publication. Here we initiate this process by identifying a number of parameters we have found to be important in microsphere-based assays designed for the quantification of low abundant genes which are variable between studies

Read-Right: a "web app" that improves reading speeds in patients with hemianopia

Effective behavioral therapies exist for patients with brain injury. The main issue is one of access. Can the internet be used as a resource so that suitable patients can build up enough practice to improve? We tested this hypothesis using a web-based application for patients with a right-sided hemianopia causing slow text reading. We studied 33 patients aged 26-81 years who fitted the entry criteria and accessed the therapy website between May 2010 and December 2011, in a longitudinal cohort study. The therapy consisted of reading animated, laterally scrolling text whose content and form was selected by the patients. Reading speeds on static text (main outcome) were assessed after every 5-h period of practice had been accrued. Statistical analysis was carried out using a repeated measures ANOVA. Read-Right therapy produced significant improvements in text reading speeds at all time points with a clear dose effect: 10 % at 5 h, 20 % at 10 h, 39 % at 15 h and 46 % at 20 h. Sub-analyses demonstrated that this was unlikely to be due to either multiple exposure to the testing materials (familiarity) or to the simple passage of time. This is the first example of a clinically proven therapy being delivered effectively to stroke patients over the internet. As therapists' time is more limited than patients' capacity to improve, carefully designed, web-based resources like Read-Right represent a realistic way of delivering a sufficient therapy dose to patients so they can obtain clinically meaningful improvements

Navigation of Distinct Euclidean Particles via Hierarchical Clustering

We present a centralized online (completely reactive) hybrid navigation algorithm for bringing a swarm of n perfectly sensed and actuated point particles in Euclidean d space (for arbitrary n and d) to an arbitrary goal configuration with the guarantee of no collisions along the way. Our construction entails a discrete abstraction of configurations using cluster hierarchies, and relies upon two prior recent constructions: (i) a family of hierarchy-preserving control policies and (ii) an abstract discrete dynamical system for navigating through the space of cluster hierarchies. Here, we relate the (combinatorial) topology of hierarchical clusters to the (continuous) topology of configurations by constructing “portals” — open sets of configurations supporting two adjacent hierarchies. The resulting online sequential composition of hierarchy-invariant swarming followed by discrete selection of a hierarchy “closer” to that of the destination along with its continuous instantiation via an appropriate portal configuration yields a computationally effective construction for the desired navigation policy

Alterations in vascular function in primary aldosteronism - a cardiovascular magnetic resonance imaging study

Introduction: Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV).<p></p> Methods: We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass.<p></p> Results: Subjects with PA had significantly lower aortic distensibilty and higher PWV compared to EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including aging. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular aging. As expected, aortic distensibility and PWV were closely correlated.<p></p> Conclusion: These results demonstrate that PA patients display increased arterial stiffness compared to EH, independent of vascular aging. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study.<p></p&gt

Polynomial Growth Harmonic Functions on Finitely Generated Abelian Groups

In the present paper, we develop geometric analytic techniques on Cayley graphs of finitely generated abelian groups to study the polynomial growth harmonic functions. We develop a geometric analytic proof of the classical Heilbronn theorem and the recent Nayar theorem on polynomial growth harmonic functions on lattices \mathds{Z}^n that does not use a representation formula for harmonic functions. We also calculate the precise dimension of the space of polynomial growth harmonic functions on finitely generated abelian groups. While the Cayley graph not only depends on the abelian group, but also on the choice of a generating set, we find that this dimension depends only on the group itself.Comment: 15 pages, to appear in Ann. Global Anal. Geo

Upper atmospheres and ionospheres of planets and satellites

The upper atmospheres of the planets and their satellites are more directly exposed to sunlight and solar wind particles than the surface or the deeper atmospheric layers. At the altitudes where the associated energy is deposited, the atmospheres may become ionized and are referred to as ionospheres. The details of the photon and particle interactions with the upper atmosphere depend strongly on whether the object has anintrinsic magnetic field that may channel the precipitating particles into the atmosphere or drive the atmospheric gas out to space. Important implications of these interactions include atmospheric loss over diverse timescales, photochemistry and the formation of aerosols, which affect the evolution, composition and remote sensing of the planets (satellites). The upper atmosphere connects the planet (satellite) bulk composition to the near-planet (-satellite) environment. Understanding the relevant physics and chemistry provides insight to the past and future conditions of these objects, which is critical for understanding their evolution. This chapter introduces the basic concepts of upper atmospheres and ionospheres in our solar system, and discusses aspects of their neutral and ion composition, wind dynamics and energy budget. This knowledge is key to putting in context the observations of upper atmospheres and haze on exoplanets, and to devise a theory that explains exoplanet demographics.Comment: Invited Revie

Effect of early and current Helicobacter pylori infection on the risk of anaemia in 6.5-year-old Ethiopian children

Background: Epidemiological and clinical studies in high income countries have suggested that Helicobacter pylori (H. pylori) may cause anaemia, but evidence is lacking from low income countries.We examined associations between H. pylori infection in early childhood and anaemia at the age of 6.5 years in an Ethiopian birth cohort. Methods: In 2011/12, 856 children (85.1 % of the 1006 original singletons in a population-based birth cohort) were followed up at age six and half. An interviewer-led questionnaire administered to mothers provided information on demographic and lifestyle variables. Haemoglobin level and red cell indices were examined using an automated haematological analyzer (Cell Dyn 1800, Abbott, USA), and stool samples analyzed for H. pylori antigen. The independent effects of H. pylori infection (measured at age 3.5 and 6.5 years) on anaemia, haemoglobin level, and red cell indices (measured at age 6.5 years) were determined using multiple logistic and linear regression. Results: The prevalence of anemia was 34.8 % (257/739), and the mean (SD) haemoglobin concentration was 11.8 (1.1) gm/dl. Current H. pylori infection at age 6.5 years was positively, though not significantly related to prevalence of anaemia (adjusted OR, 95 % CI, 1.15; 0.69, 1.93, p = 0.59). Any H. pylori infection up to age 6.5 years was significantly associated with an increased risk of anaemia at age 6.5 (adjusted OR, 95 % CI, 1.68; 1.22, 2.32, p = 0.01). A significant reduction in haemoglobin concentration and red cell indices was also observed among children who had any H. pylori infection up to age 6.5 (Hb adjusted β = −0.19, 95 % CI, −0.35 to −0.03, p = 0.01; MCV adjusted β = −2.22, 95 % CI, −3.43 to −1.01, p = 0.01; MCH adjusted β = −0.63, 95 % CI, −1.15 to - 0.12, p = 0.01; and MCHC adjusted β = −0.67, 95 % CI, −1.21 to −0.14, p = 0.01), respectively. Conclusion: This study provides further evidence from a low income country that any H. pylori infection up to age 6.5 is associated with higher prevalence of anaemia, and reduction of haemoglobin level and red cell indices at age 6.5

First-principles study of illite-smectite and implications for clay mineral systems

Illite-smectite interstratified clay minerals are ubiquitous in sedimentary basins and they have been linked to the maturation, migration and trapping of hydrocarbons(1), rock cementation(2), evolution of porewater chemistry during diagenesis(3) and the development of pore pressure(4). But, despite the importance of these clays, their structures are controversial. Two competing models exist, each with profoundly different consequences for the understanding of diagenetic processes: model A views such interstratified clays as a stacking of layers identical to endmember illite and smectite layers, implying discrete and independently formed units (fundamental particles)(5), whereas model B views the clays as composed of crystallites with a unique structure that maintains coherency over much greater distances, in line with local charge balance about interlayers(6). Here we use first-principles density-functional theory to explore the energetics and structures of these two models for an illite-smectite interstratified clay mineral with a ratio of 1:1 and a Reichweite parameter of 1. We find that the total energy of model B is 2.3 kJ atom(-1) mol(-1) lower than that of model A, and that this energy difference can be traced to structural distortions in model A due to local charge imbalance. The greater stability of model B requires re-evaluation of the evolution of the smectite-to-illite sequence of clay minerals, including the nature of coexisting species, stability relations, growth mechanisms and the model of fundamental particles.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62760/1/nature01155.pd