Measurement error in a multi-level analysis of air pollution and health: a simulation study.

BACKGROUND: Spatio-temporal models are increasingly being used to predict exposure to ambient outdoor air pollution at high spatial resolution for inclusion in epidemiological analyses of air pollution and health. Measurement error in these predictions can nevertheless have impacts on health effect estimation. Using statistical simulation we aim to investigate the effects of such error within a multi-level model analysis of long and short-term pollutant exposure and health. METHODS: Our study was based on a theoretical sample of 1000 geographical sites within Greater London. Simulations of "true" site-specific daily mean and 5-year mean NO2 and PM10 concentrations, incorporating both temporal variation and spatial covariance, were informed by an analysis of daily measurements over the period 2009-2013 from fixed location urban background monitors in the London area. In the context of a multi-level single-pollutant Poisson regression analysis of mortality, we investigated scenarios in which we specified: the Pearson correlation between modelled and "true" data and the ratio of their variances (model versus "true") and assumed these parameters were the same spatially and temporally. RESULTS: In general, health effect estimates associated with both long and short-term exposure were biased towards the null with the level of bias increasing to over 60% as the correlation coefficient decreased from 0.9 to 0.5 and the variance ratio increased from 0.5 to 2. However, for a combination of high correlation (0.9) and small variance ratio (0.5) non-trivial bias (> 25%) away from the null was observed. Standard errors of health effect estimates, though unaffected by changes in the correlation coefficient, appeared to be attenuated for variance ratios > 1 but inflated for variance ratios < 1. CONCLUSION: While our findings suggest that in most cases modelling errors result in attenuation of the effect estimate towards the null, in some situations a non-trivial bias away from the null may occur. The magnitude and direction of bias appears to depend on the relationship between modelled and "true" data in terms of their correlation and the ratio of their variances. These factors should be taken into account when assessing the validity of modelled air pollution predictions for use in complex epidemiological models

Effective Field Theory and Finite Density Systems

This review gives an overview of effective field theory (EFT) as applied at finite density, with a focus on nuclear many-body systems. Uniform systems with short-range interactions illustrate the ingredients and virtues of many-body EFT and then the varied frontiers of EFT for finite nuclei and nuclear matter are surveyed.Comment: 27 pages, 5 figure

An unusual case of finger swelling: A case report

A 66 year old man initially presented with haemoptysis and subsequently required a pneumonectomy for a lung mass, following this he had a finger swelling which was found to be a rare leiomyosarcoma and this was a metastatic deposit. This pattern of metastasis for this type of tumour has not been described before

Role of pyrite in formation of hydroxyl radicals in coal: possible implications for human health

BACKGROUND: The harmful effects from inhalation of coal dust are well-documented. The prevalence of lung disease varies by mining region and may, in part, be related to regional differences in the bioavailable iron content of the coal. Pyrite (FeS(2)), a common inorganic component in coal, has been shown to spontaneously form reactive oxygen species (ROS) (i.e., hydrogen peroxide and hydroxyl radicals) and degrade nucleic acids. This raises the question regarding the potential for similar reactivity from coal that contains pyrite. Experiments were performed to specifically evaluate the role of pyrite in coal dust reactivity. Coal samples containing various amounts of FeS(2 )were compared for differences in their generation of ROS and degradation of RNA. RESULTS: Coals that contain iron also show the presence of FeS(2), generate ROS and degrade RNA. Coal samples that do not contain pyrite do not produce ROS nor degrade RNA. The concentration of generated ROS and degradation rate of RNA both increase with greater FeS(2 )content in the coals. CONCLUSION: The prevalence of coal workers' pneumoconiosis can be correlated to the amount of FeS(2 )in the coals. Considering the harmful effects of generation of ROS by inhaled particles, the results presented here show a possible mechanism whereby coal samples may contribute to CWP. This suggests that the toxicity of coal may be explained, in part, by the presence of FeS(2)

How Filaments are Woven into the Cosmic Web

Observations indicate galaxies are distributed in a filament-dominated web-like structure. Numerical experiments at high and low redshift of viable structure formation theories also show filament-dominance. We present a simple quantitative explanation of why this is so, showing that the final-state web is actually present in embryonic form in the overdensity pattern of the initial fluctuations, with nonlinear dynamics just sharpening the image. The web is largely defined by the position and primordial tidal fields of rare events in the medium, with the strongest filaments between nearby clusters whose tidal tensors are nearly aligned. Applications of the cosmic web theory to observations include probing cluster-cluster bridges by weak gravitational lensing, X-rays, and the Sunyaev-Zeldovich effect and probing high redshift galaxy-galaxy bridges by low column density Lyman alpha absorption lines.Comment: 9 pages, gzipped uuencoded postscript file, 4 figures in separate files. The text + figures are also available from anonymous ftp site: ftp://ftp.cita.utoronto.ca/ftp/cita/bond/bkp_natur

Making a splash with water repellency

A 'splash' is usually heard when a solid body enters water at large velocity. This phenomena originates from the formation of an air cavity resulting from the complex transient dynamics of the free interface during the impact. The classical picture of impacts on free surfaces relies solely on fluid inertia, arguing that surface properties and viscous effects are negligible at sufficiently large velocities. In strong contrast to this large-scale hydrodynamic viewpoint, we demonstrate in this study that the wettability of the impacting body is a key factor in determining the degree of splashing. This unexpected result is illustrated in Fig.1: a large cavity is evident for an impacting hydrophobic sphere (1.b), contrasting with the hydrophilic sphere's impact under the very same conditions (1.a). This unforeseen fact is furthermore embodied in the dependence of the threshold velocity for air entrainment on the contact angle of the impacting body, as well as on the ratio between the surface tension and fluid viscosity, thereby defining a critical capillary velocity. As a paradigm, we show that superhydrophobic impacters make a big 'splash' for any impact velocity. This novel understanding provides a new perspective for impacts on free surfaces, and reveals that modifications of the detailed nature of the surface -- involving physico-chemical aspects at the nanometric scales -- provide an efficient and versatile strategy for controlling the water entry of solid bodies at high velocity.Comment: accepted for publication in Nature Physic

Partial duplication of the PRLR and SPEF2 genes at the late feathering locus in chicken

Background One of the loci responsible for feather development in chickens is K. The K allele is partially dominant to the k+ allele and causes a retard in the emergence of flight feathers at hatch. The K locus is sex linked and located on the Z chromosome. Therefore, the locus can be utilized to produce phenotypes that identify the sexes of chicks at hatch. Previous studies on the organization of the K allele concluded the integration of endogenous retrovirus 21 (ev21) into one of two large homologous segments located on the Z chromosome of late feathering chickens. In this study, a detailed molecular analysis of the K locus and a DNA test to distinguish between homozygous and heterozygous late feathering males are presented. Results The K locus was investigated with quantitative PCR by examining copy number variations in a total of fourteen markers surrounding the ev21 integration site. The results showed a duplication at the K allele and sequence analysis of the breakpoint junction indicated a tandem duplication of 176,324 basepairs. The tandem duplication of this region results in the partial duplication of two genes; the prolactin receptor and the gene encoding sperm flagellar protein 2. Sequence analysis revealed that the duplication is similar in Broiler and White Leghorn. In addition, twelve late feathering animals, including Broiler, White Leghorn, and Brown Layer lines, contained a 78 bp breakpoint junction fragment, indicating that the duplication is similar in all breeds. The breakpoint junction was used to develop a TaqMan-based quantitative PCR test to allow distinction between homozygous and heterozygous late feathering males. In total, 85.3% of the animals tested were correctly assigned, 14.7% were unassigned and no animals were incorrectly assigned. Conclusion The detailed molecular analysis presented in this study revealed the presence of a tandem duplication in the K allele. The duplication resulted in the partial duplication of two genes; the prolactin receptor and the gene encoding sperm flagellar protein 2. Furthermore, a DNA test was developed to distinguish between homozygous and heterozygous late feathering males

Patient-Reported Satisfaction and Study Drug Discontinuation: Post-Hoc Analysis of Findings from ROCKET AF.

IntroductionPatient-reported outcomes (PROs) and satisfaction endpoints are increasingly important in clinical trials and may be associated with treatment adherence. In this post hoc substudy from ROCKET AF, we examined whether patient-reported satisfaction was associated with study drug discontinuation.MethodsROCKET AF (n = 14,264) compared rivaroxaban with warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation. We analyzed treatment satisfaction scores: the Anti-Clot Treatment Scale (ACTS) and Treatment Satisfaction Questionnaire for Medication version II (TSQM II). We compared satisfaction with study drug between the two treatment arms, and examined the association between satisfaction and patient-driven study drug discontinuation (stopping study drug due to withdrawal of consent, noncompliance, or loss to follow-up).ResultsA total of 1577 (11%) patients participated in the Patient Satisfaction substudy; 1181 (8.3%) completed both the ACTS and TSQM II 4 weeks after starting study drug. Patients receiving rivaroxaban did not experience significant differences in satisfaction compared with those receiving warfarin. During a median follow-up of 1.6 years, 448 premature study drug discontinuations occurred (213 rivaroxaban group; 235 warfarin group), of which 116 (26%) were patient-driven (52 [24%] rivaroxaban group; 64 [27%] warfarin group). No significant differences were observed between satisfaction level and rates of patient-driven study drug discontinuation.ConclusionsStudy drug satisfaction did not predict rate of study drug discontinuation. No significant difference was observed between satisfaction with warfarin and rivaroxaban, as expected given the double-blind trial design. Although these results are negative, the importance of PRO data will only increase, and these analyses may inform future studies that explore the relationship between drug-satisfaction PROs, adherence, and clinical outcomes. CLINICALTRIALS.GOV: NCT00403767.FundingThe ROCKET AF trial was funded by Johnson &amp; Johnson and Bayer

Coordinated Groundâ Based and Spaceâ Based Observations of Equatorial Plasma Bubbles

This paper presents coordinated and fortuitous groundâ based and spaceborne observations of equatorial plasma bubbles (EPBs) over the South American area on 24 October 2018, combining the following measurements: Globalâ scale Observations of Limb and Disk far ultraviolet emission images, Global Navigation Satellite System total electron content data, Swarm in situ plasma density observations, ionosonde virtual height and drift data, and cloud brightness temperature data. The new observations from the Globalâ scale Observations of Limb and Disk/ultraviolet imaging spectrograph taken at geostationary orbit provide a unique opportunity to image the evolution of plasma bubbles near the F peak height over a large geographic area from a fixed longitude location. The combined multiâ instrument measurements provide a more integrated and comprehensive way to study the morphological structure, development, and seeding mechanism of EPBs. The main results of this study are as follows: (1) The bubbles developed a westward tilted structure with 10â 15° inclination relative to the local geomagnetic field lines, with eastward drift velocity of 80â 120 m/s near the magnetic equator that gradually decreased with increasing altitude/latitude. (2) Waveâ like oscillations in the bottomside F layer and detrended total electron content were observed, which are probably due to upward propagating atmospheric gravity waves. The wavelength based on the mediumâ scale traveling ionospheric disturbance signature was consistent with the interbubble distance of â ¼500â 800 km. (3) The atmospheric gravity waves that originated from tropospheric convective zone are likely to play an important role in seeding the development of this equatorial EPBs event.Plain Language SummaryThis study presents multiâ instrument observations of equatorial plasma density depletions occurred on 24 October 2018 by using Globalâ scale Observations of Limb and Disk far ultraviolet images, Global Navigation Satellite System total electron content data, electron density measurements from Swarm satellite, ionosonde measurements, and cloud temperature data. This multiâ instrument study generated an integrated and detailed image revealing both largeâ scale and mesoscale structures of the equatorial plasma depletion. Our results also suggest that atmospheric gravity waves originating from tropospheric convection activity could play a significant seeding role in the development of equatorial plasma bubbles.Key PointsCombined GOLD/UV spectrograph images and groundâ based TEC data revealed EPB features and development over a large geographic areaBottomside F layer oscillations and traveling ionospheric disturbance were observed by ionosonde and detrended TEC resultsAtmospheric gravity waves likely play an important role in seeding the Râ T instability and the development of this EPB eventPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153570/1/jgra55456_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153570/2/jgra55456.pd

Mitochondria and Quality Control Defects in a Mouse Model of Gaucher Disease-Links to Parkinson's Disease

Mutations in the glucocerebrosidase (gba) gene cause Gaucher disease (GD), the most common lysosomal storage disorder, and increase susceptibility to Parkinson’s disease (PD). While the clinical and pathological features of idiopathic PD and PD related to gba (PD-GBA) mutations are very similar, cellular mechanisms underlying neurodegeneration in each are unclear. Using a mouse model of neuronopathic GD, we show that autophagic machinery and proteasomal machinery are defective in neurons and astrocytes lacking gba. Markers of neurodegeneration—p62/SQSTM1, ubiquitinated proteins, and insoluble α-synuclein—accumulate. Mitochondria were dysfunctional and fragmented, with impaired respiration, reduced respiratory chain complex activities, and a decreased potential maintained by reversal of the ATP synthase. Thus a primary lysosomal defect causes accumulation of dysfunctional mitochondria as a result of impaired autophagy and dysfunctional proteasomal pathways. These data provide conclusive evidence for mitochondrial dysfunction in GD and provide insight into the pathogenesis of PD and PD-GBA