Comparison of breath-hold, respiratory navigated and free-breathing MR elastography of the liver

$\textit{Purpose:}$ Hepatic magnetic resonance elastography (MRE) is currently a breath-hold imaging technique. Patients with chronic liver disease can have comorbidities that limit their ability to breath-hold (BH) for the required acquisition time. Our aim was to evaluate whether stiffness measurements obtained from a navigator-triggered MRE acquisition are comparable to standard expiratory breath-hold, inspiratory breath-hold or free-breathing in healthy participants. $\textit{Materials and methods:}$ Twelve healthy participants were imaged using the four methods on a clinical 1.5 T MR system equipped with a product MRE system. Mean liver stiffness, and measurable area of stiffness (with a confidence threshold >95%) were compared between sequences using the concordance correlation coefficient. Repeatability of each sequence between two acquisitions was also assessed. $\textit{Results:}$ The standard BH expiratory technique had high concordance with the navigated technique (r = 0.716), and low concordance with the BH inspiration (r = 0.165) and free-breathing (r = 0.105) techniques. The navigator-triggered technique showed no statistical difference in measurable area of liver or in repeatability compared with the standard expiratory acquisition (p = 0.997 and p = 0.407 respectively). The free-breathing technique produced less measurable liver area and was less repeatable than the alternative techniques. The increase in acquisition time for navigator techniques was 3 min 6 s compared to standard expiratory breath-hold. $\textit{Conclusion:}$ Navigator-based hepatic MRE measurements are comparable to the reference standard expiratory breath-hold acquisition in healthy participants.This work was supported by the Addenbrooke's Charitable Trust and the NIHR Comprehensive Biomedical Research Centre award to Cambridge University Hospitals NHS Foundation Trust in partnership with the University of Cambridge

Amniotic fluid volume: Rapid MR-based assessment at 28-32 weeks gestation.

OBJECTIVES: This work evaluates rapid magnetic resonance projection hydrography (PH) based amniotic fluid volume (AFV) estimates against established routine ultrasound single deepest vertical pocket (SDVP) and amniotic fluid index (AFI) measurements, in utero at 28-32 weeks gestation. Manual multi-section planimetry (MSP) based measurement of AFV is used as a proxy reference standard. METHODS: Thirty-five women with a healthy singleton pregnancy (20-41 years) attending routine antenatal ultrasound were recruited. SDVP and AFI were measured using ultrasound, with same day MRI assessing AFV with PH and MSP. The relationships between the respective techniques were assessed using linear regression analysis and Bland-Altman method comparison statistics. RESULTS: When comparing estimated AFV, a highly significant relationship was observed between PH and the reference standard MSP (R(2) = 0.802, p < 0.001). For the US measurements, SDVP measurement related most closely to amniotic fluid volume, (R(2) = 0.470, p < 0.001), with AFI demonstrating a weaker relationship (R(2) = 0.208, p = 0.007). CONCLUSION: This study shows that rapid MRI based PH measurement is a better predictor of AFV, relating more closely to our proxy standard than established US techniques. Although larger validation studies across a range of gestational ages are required this approach could form part of MR fetal assessment, particularly where poly- or oligohydramnios is suspected. KEY POINTS: • MR projection hydrography can be used to estimate amniotic fluid volume. • MR projection hydrography relies on the T2w signal from amniotic fluid. • Amniotic fluid volume (AFV) is more accurately assessed than with ultrasound.This study was supported by the National Institute of Health Research, Cambridge Biomedical Research Centre. The authors also acknowledge the support of Addenbrooke’s Charitable Trust and thank the participants for their contribution to the study.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00330-015-4179-

The Dynamics of Nestedness Predicts the Evolution of Industrial Ecosystems

In economic systems, the mix of products that countries make or export has been shown to be a strong leading indicator of economic growth. Hence, methods to characterize and predict the structure of the network connecting countries to the products that they export are relevant for understanding the dynamics of economic development. Here we study the presence and absence of industries at the global and national levels and show that these networks are significantly nested. This means that the less filled rows and columns of these networks' adjacency matrices tend to be subsets of the fuller rows and columns. Moreover, we show that nestedness remains relatively stable as the matrices become more filled over time and that this occurs because of a bias for industries that deviate from the networks' nestedness to disappear, and a bias for the missing industries that reduce nestedness to appear. This makes the appearance and disappearance of individual industries in each location predictable. We interpret the high level of nestedness observed in these networks in the context of the neutral model of development introduced by Hidalgo and Hausmann (2009). We show that, for the observed fills, the model can reproduce the high level of nestedness observed in these networks only when we assume a high level of heterogeneity in the distribution of capabilities available in countries and required by products. In the context of the neutral model, this implies that the high level of nestedness observed in these economic networks emerges as a combination of both, the complementarity of inputs and heterogeneity in the number of capabilities available in countries and required by products. The stability of nestedness in industrial ecosystems, and the predictability implied by it, demonstrates the importance of the study of network properties in the evolution of economic networks.Comment: 26 page

Accurate Liability Estimation Improves Power in Ascertained Case Control Studies

Linear mixed models (LMMs) have emerged as the method of choice for confounded genome-wide association studies. However, the performance of LMMs in non-randomly ascertained case-control studies deteriorates with increasing sample size. We propose a framework called LEAP (Liability Estimator As a Phenotype, https://github.com/omerwe/LEAP) that tests for association with estimated latent values corresponding to severity of phenotype, and demonstrate that this can lead to a substantial power increase

What lies beneath: A comparison of reading aloud in pure alexia and semantic dementia

Exaggerated effects of word length upon reading aloud performance define Pure Alexia, but have also been observed in Semantic Dementia. Some researchers have proposed a readingspecific account, whereby performance in these two disorders reflects the same cause: impaired orthographic processing. In contrast, according to the primary systems view of acquired reading disorders, Pure Alexia results from a basic visual processing deficit, whereas degraded semantic knowledge undermines reading performance in Semantic Dementia. To explore the source of reading deficits in these two disorders, we compared the reading performance of 10 Pure Alexic and 10 Semantic Dementia patients, matched in terms of overall severity of reading deficit. The results revealed comparable frequency effects on reading accuracy, but weaker effects of regularity in Pure Alexia than Semantic Dementia. Analysis of error types revealed a higher rate of letter-based errors and a lower rate of regularisation responses in Pure Alexia than Semantic Dementia. Error responses were most often words in Pure Alexia but most often nonwords in Semantic Dementia. Although all patients made some letter substitution errors, these were characterised by visual similarity in Pure Alexia and phonological similarity in Semantic Dementia. Overall, the data indicate that the reading deficits in Pure Alexia and Semantic Dementia arise from impairments of visual processing and knowledge of word meaning, respectively. The locus and mechanisms of these impairments are placed within the context of current connectionist models of reading

Laser cooling of a diatomic molecule

It has been roughly three decades since laser cooling techniques produced ultracold atoms, leading to rapid advances in a vast array of fields. Unfortunately laser cooling has not yet been extended to molecules because of their complex internal structure. However, this complexity makes molecules potentially useful for many applications. For example, heteronuclear molecules possess permanent electric dipole moments which lead to long-range, tunable, anisotropic dipole-dipole interactions. The combination of the dipole-dipole interaction and the precise control over molecular degrees of freedom possible at ultracold temperatures make ultracold molecules attractive candidates for use in quantum simulation of condensed matter systems and quantum computation. Also ultracold molecules may provide unique opportunities for studying chemical dynamics and for tests of fundamental symmetries. Here we experimentally demonstrate laser cooling of the molecule strontium monofluoride (SrF). Using an optical cycling scheme requiring only three lasers, we have observed both Sisyphus and Doppler cooling forces which have substantially reduced the transverse temperature of a SrF molecular beam. Currently the only technique for producing ultracold molecules is by binding together ultracold alkali atoms through Feshbach resonance or photoassociation. By contrast, different proposed applications for ultracold molecules require a variety of molecular energy-level structures. Our method provides a new route to ultracold temperatures for molecules. In particular it bridges the gap between ultracold temperatures and the ~1 K temperatures attainable with directly cooled molecules (e.g. cryogenic buffer gas cooling or decelerated supersonic beams). Ultimately our technique should enable the production of large samples of molecules at ultracold temperatures for species that are chemically distinct from bialkalis.Comment: 10 pages, 7 figure

Multicolour correlative imaging using phosphor probes

Correlative light and electron microscopy exploits the advantages of optical methods, such as multicolour probes and their use in hydrated live biological samples, to locate functional units, which are then correlated with structural details that can be revealed by the superior resolution of electron microscopes. One difficulty is locating the area imaged by the electron beam in the much larger optical field of view. Multifunctional probes that can be imaged in both modalities and thus register the two images are required. Phosphor materials give cathodoluminescence (CL) optical emissions under electron excitation. Lanthanum phosphate containing thulium or terbium or europium emits narrow bands in the blue, green and red regions of the CL spectrum; they may be synthesised with very uniform-sized crystals in the 10- to 50-nm range. Such crystals can be imaged by CL in the electron microscope, at resolutions limited by the particle size, and with colour discrimination to identify different probes. These materials also give emissions in the optical microscope, by multiphoton excitation. They have been deposited on the surface of glioblastoma cells and imaged by CL. Gadolinium oxysulphide doped with terbium emits green photons by either ultraviolet or electron excitation. Sixty-nanometre crystals of this phosphor have been imaged in the atmospheric scanning electron microscope (JEOL ClairScope). This probe and microscope combination allow correlative imaging in hydrated samples. Phosphor probes should prove to be very useful in correlative light and electron microscopy, as fiducial markers to assist in image registration, and in high/super resolution imaging studies

Mobile phone text messaging intervention to improve alertness and reduce sleepiness and fatigue during shiftwork among emergency medicine clinicians: Study protocol for the SleepTrackTXT pilot randomized controlled trial

Background: Mental and physical fatigue while at work is common among emergency medical services (EMS) shift workers. Extended shifts (for example 24 hours) and excessive amounts of overtime work increase the likelihood of negative safety outcomes and pose a challenge for EMS fatigue-risk management. Text message-based interventions are a potentially high-impact, low-cost platform for sleep and fatigue assessment and distributing information to workers at risk of negative safety outcomes related to sleep behaviors and fatigue.Methods/Design: We will conduct a pilot randomized trial with a convenience sample of adult EMS workers recruited from across the United States using a single study website. Participants will be allocated to one of two possible arms for a 90-day study period. The intervention arm will involve text message assessments of sleepiness, fatigue, and difficulty with concentration at the beginning, during, and end of scheduled shifts. Intervention subjects reporting high levels of sleepiness or fatigue will receive one of four randomly selected intervention messages promoting behavior change during shiftwork. Control subjects will receive assessment only text messages. We aim to determine the performance characteristics of a text messaging tool for the delivery of a sleep and fatigue intervention. We seek to determine if a text messaging program with tailored intervention messages is effective at reducing perceived sleepiness and/or fatigue among emergency medicine clinician shift workers. Additional aims include testing whether a theory-based behavioral intervention, delivered by text message, changes 'alertness behaviors'.Discussion: The SleepTrackTXT pilot trial could provide evidence of compliance and effectiveness that would support rapid widespread expansion in one of two forms: 1) a stand-alone program in the form of a tailored/individualized sleep monitoring and fatigue reduction support service for EMS workers; or 2) an add-on to a multi-component fatigue risk management program led and maintained by employers or by safety and risk management services.Trial Registration: Clinicaltrials.gov NCT02063737, Registered on 10 January 2014. © 2014 Patterson et al

The geography of recent genetic ancestry across Europe

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of recent genealogical ancestry over the past three thousand years at a continental scale. We detected 1.9 million shared genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 10-50 genetic common ancestors from the last 1500 years, and upwards of 500 genetic ancestors from the previous 1000 years. These numbers drop off exponentially with geographic distance, but since genetic ancestry is rare, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1000 years. There is substantial regional variation in the number of shared genetic ancestors: especially high numbers of common ancestors between many eastern populations likely date to the Slavic and/or Hunnic expansions, while much lower levels of common ancestry in the Italian and Iberian peninsulas may indicate weaker demographic effects of Germanic expansions into these areas and/or more stably structured populations. Recent shared ancestry in modern Europeans is ubiquitous, and clearly shows the impact of both small-scale migration and large historical events. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world.Comment: Full size figures available from http://www.eve.ucdavis.edu/~plralph/research.html; or html version at http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm