MRI of the lung (1/3):methods

Proton magnetic resonance imaging (MRI) has recently emerged as a clinical tool to image the lungs. This paper outlines the current technical aspects of MRI pulse sequences, radiofrequency (RF) coils and MRI system requirements needed for imaging the pulmonary parenchyma and vasculature. Lung MRI techniques are presented as a “technical toolkit”, from which MR protocols will be composed in the subsequent papers for comprehensive imaging of lung disease and function (parts 2 and 3). This paper is pitched at MR scientists, technicians and radiologists who are interested in understanding and establishing lung MRI methods. Images from a 1.5 T scanner are used for illustration of the sequences and methods that are highlighted. Main Messages • Outline of the hardware and pulse sequence requirements for proton lung MRI • Overview of pulse sequences for lung parenchyma, vascular and functional imaging with protons • Demonstration of the pulse-sequence building blocks for clinical lung MRI protocol

The Inflammatory Response to Double Stranded DNA in Endothelial Cells Is Mediated by NFκB and TNFα

Endothelial cells represent an important barrier between the intravascular compartment and extravascular tissues, and therefore serve as key sensors, communicators, and amplifiers of danger signals in innate immunity and inflammation. Double stranded DNA (dsDNA) released from damaged host cells during injury or introduced by pathogens during infection, has emerged as a potent danger signal. While the dsDNA-mediated immune response has been extensively studied in immune cells, little is known about the direct and indirect effects of dsDNA on the vascular endothelium. In this study we show that direct dsDNA stimulation of endothelial cells induces a potent proinflammatory response as demonstrated by increased expression of ICAM1, E-selectin and VCAM1, and enhanced leukocyte adhesion. This response was dependent on the stress kinases JNK and p38 MAPK, required the activation of proinflammatory transcription factors NFκB and IRF3, and triggered the robust secretion of TNFα for sustained secondary activation of the endothelium. DNA-induced TNFα secretion proved to be essential in vivo, as mice deficient in the TNF receptor were unable to mount an acute inflammatory response to dsDNA. Our findings suggest that the endothelium plays an active role in mediating dsDNA-induced inflammatory responses, and implicate its importance in establishing an acute inflammatory response to sterile injury or systemic infection, where host or pathogen derived dsDNA may serve as a danger signal.United States. Dept. of Defense (CDMRP Predoctoral Training Award)National Institutes of Health (U.S.) (NIH BioMEMS Resource Center Grant P41 EB-002503)National Institutes of Health (U.S.) (NIH Grant RO1AI063795)Shriners Hospital for Childre

Using high angular resolution diffusion imaging data to discriminate cortical regions

Brodmann's 100-year-old summary map has been widely used for cortical localization in neuroscience. There is a pressing need to update this map using non-invasive, high-resolution and reproducible data, in a way that captures individual variability. We demonstrate here that standard HARDI data has sufficiently diverse directional variation among grey matter regions to inform parcellation into distinct functional regions, and that this variation is reproducible across scans. This characterization of the signal variation as non-random and reproducible is the critical condition for successful cortical parcellation using HARDI data. This paper is a first step towards an individual cortex-wide map of grey matter microstructure, The gray/white matter and pial boundaries were identified on the high-resolution structural MRI images. Two HARDI data sets were collected from each individual and aligned with the corresponding structural image. At each vertex point on the surface tessellation, the diffusion-weighted signal was extracted from each image in the HARDI data set at a point, half way between gray/white matter and pial boundaries. We then derived several features of the HARDI profile with respect to the local cortical normal direction, as well as several fully orientationally invariant features. These features were taken as a fingerprint of the underlying grey matter tissue, and used to distinguish separate cortical areas. A support-vector machine classifier, trained on three distinct areas in repeat 1 achieved 80-82% correct classification of the same three areas in the unseen data from repeat 2 in three volunteers. Though gray matter anisotropy has been mostly overlooked hitherto, this approach may eventually form the foundation of a new cortical parcellation method in living humans. Our approach allows for further studies on the consistency of HARDI based parcellation across subjects and comparison with independent microstructural measures such as ex-vivo histology

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Early influences on cardiovascular and renal development

The hypothesis that a developmental component plays a role in subsequent disease initially arose from epidemiological studies relating birth size to both risk factors for cardiovascular disease and actual cardiovascular disease prevalence in later life. The findings that small size at birth is associated with an increased risk of cardiovascular disease have led to concerns about the effect size and the causality of the associations. However, recent studies have overcome most methodological flaws and suggested small effect sizes for these associations for the individual, but an potential important effect size on a population level. Various mechanisms underlying these associations have been hypothesized, including fetal undernutrition, genetic susceptibility and postnatal accelerated growth. The specific adverse exposures in fetal and early postnatal life leading to cardiovascular disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life may underlie the complex associations of fetal growth retardation and low birth weight with cardiovascular disease in later life. To estimate the population effect size and to identify the underlying mechanisms, well-designed epidemiological studies are needed. This review is focused on specific adverse fetal exposures, cardiovascular adaptations and perspectives for new studies. Copyrigh

Search for new physics in the multijet and missing transverse momentum final state in proton-proton collisions at √s=8 Tev

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Measurement of Higgs boson production and properties in the WW decay channel with leptonic final states

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Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants

BACKGROUND: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. METHODS: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence—defined as fasting plasma glucose of 7·0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs—in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. FINDINGS: We used data from 751 studies including 4 372 000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4·3% (95% credible interval 2·4–7·0) in 1980 to 9·0% (7·2–11·1) in 2014 in men, and from 5·0% (2·9–7·9) to 7·9% (6·4–9·7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28·5% due to the rise in prevalence, 39·7% due to population growth and ageing, and 31·8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. INTERPRETATION: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries. FUNDING: Wellcome Trust

Study of double parton scattering using W+2-jet events in proton-proton collisions at √s=7 TeV

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