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We report on the electronic and magnetic properties of superconductor-ferromagnet heterostructures fabricated by electron beam evaporation on to unheated thermally oxidised Si substrates. Polycrystalline Nb thin films (5 to 50 nm thick) were shown to possess reliably high superconducting critical temperatures ($$T_{c}$$ T c ), which correlate well with the residual resistivity ratio (RRR) of the film. These properties improved during ex-situ annealing, resulting in $${\Delta }T_{c}$$ Δ T c and $${\Delta }$$ Δ RRR increases of up 2.2 K ($$\sim$$ ∼ 40% of the pre-annealed $$T_{c}$$ T c ) and 0.8 ($$\sim$$ ∼ 60% of the pre-annealed RRR) respectively. Nb/Pt/Co/Pt heterostructures showed substantial perpendicular anisotropy in the ultrathin limit (≤ 2.5 nm), even in the extreme limit of Pt(0.8 nm)/Co(1 nm)/Pt(0.6 nm). These results point to the use of electron beam evaporation as route to line-of-sight deposited, low-thickness, high quality Nb-based superspintronic multilayers.

Objective: Personality influences many aspects of the health process. It is unclear to what extent self- and informant-reports of the Big Five offer incremental validity for the prediction of inflammatory biomarkers and whether inflammation provides a unique pathway between personality and indicators of physical health, independent of health behaviors. Methods: Using data from older adults (N = 1,630) enrolled in the St. Louis Personality and Aging Network study, we tested whether self- and informant-reported Big Five traits show unique associations with inflammation (IL-6, CRP, TNF-α). Further, we tested whether inflammation and health behaviors indirectly link personality to health-related quality of life, body mass index, and chronic disease burden using longitudinal mediation in a structural equation modeling framework.Results: Self-reports, informant-reports, and general trait factors of personality predicted future inflammatory biomarker levels (unstandardized regression coefficients ranged -0.08 to 0.07 for self, -0.13 to -0.10 for informants, and -0.16 to -0.11 for general). Additionally, all assessment methods of personality were associated with the indicators of physical health through biomarker and health behavior pathways. Effects were primarily found for conscientiousness and neuroticism; IL-6 and CRP were the biomarkers with the most indirect effects; and indirect paths overall emerged more frequently through health behaviors, but this varied by outcome.Conclusions: Self- and informant-reports provided unique predictive validity of inflammatory biomarkers. Findings highlight the benefits of using of multiple assessments of personality and the importance of examining multiple, distinct pathways by which personality might influence health to understand the mechanisms underlying this relationship more fully.

Personality traits predict both the initiation and continued usage of alcohol and drugs. Less established is if substance use is associated with subsequent changes in personality, especially during the sensitive period of adolescence. We used three approaches to disentangle selection and socialization effects to address whether substance use is associated with personality development (impulsivity, sensation-seeking, depression, self-esteem). First, we used a multi-wave longitudinal sample of adolescents (N = 8,303) from the National Longitudinal Survey of Youth - Child and Young Adult dataset to study the first use of several substances. Second, we used propensity score weighting to equate users and abstainers on a range of background variables. Third, we investigated changes before, during, and after initiation of substances. Overall, there was unique variability and effects in personality across time for average levels, trajectories, and magnitudes of change both between users and abstainers as well as within users of specific substances. Results suggest that initiation of substance use is associated with changes in personality; the specifics of which are largely contingent upon the substance being used. Impulsivity and sensation- seeking were the traits associated with the most change while cocaine and cigarettes were the substances associated with the greatest changes.

Although there have been increasing calls to recognise the ‘voice of the coach’ in both policy and research, there has been very little work that has asked the coaches directly: ‘what are your main issues and problems?’, and ‘where do you go for support’? Instead assessments and decisions have been made on these issues by the media, policy-makers, support agencies, governing bodies and researchers with results often reflecting the perspectives and interests of the latter. This paper presents new research with a reasonably representative sample of over 1,000 UK coaches that considers the issues and problems, and support networks, from the perspective of the coaches themselves. The results suggest that coaches experience a wide range of problems but that they can be broken down into 17 main categories with places to play sport (e.g. facilities), problems with player-coach interaction, and problems with coaching knowledge and skills, being most frequently mentioned. In terms of support networks, the coaches tended to look ‘closest to home’: to themselves, their family/friends, participants and parents, and local coaching networks. Governing bodies and coaching associations tend to be less well used. Some implications for policy and practice are discussed.

Purpose:Dynamic magnetic resonance spectroscopic imaging of hyperpolarized 13C-labeled cell substrates has enabled the investigation of tissue metabolism in vivo. Currently observation of these hyperpolarized substrates is limited mainly to 13C detection. We describe here an imaging pulse sequence that enables proton observation by using polarization transfer from the hyperpolarized 13C nucleus to spin-coupled protons.Methods:The pulse sequence transfers 13C hyperpolarization to 1H using a modified reverse insensitive nuclei enhanced by polarization transfer (INEPT) sequence that acquires a fully refocused echo. The resulting hyperpolarized 1H signal is acquired using a 2D echo-planar trajectory. The efficiency of polarization transfer was investigated using simulations with and without T1 and T2 relaxation of both the 1H and 13C nuclei.Results:Simulations showed that 1H detection of the hyperpolarized 13C nucleus in lactate should increase significantly the signal-to-noise ratio when compared with direct 13C detection at 3T. However the advantage of 1H detection is expected to disappear at higher fields. Dynamic 1H images of hyperpolarized [1-13C]lactate, with a spatial resolution of 1.25 × 1.25 mm2, were acquired from a phantom injected with hyperpolarized [1-13C]lactate and from tumors in vivo following injection of hyperpolarized [1-13C]pyruvate.Conclusions:The sequence allows 1H imaging of hyperpolarized 13C-labeled substrates in vivo. Magn Reson Med, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

This paper describes our approach to construct a scalable system for unsupervised information extraction from the behaviour change intervention literature. Due to the many different types of attribute to be extracted, we adopt a passage retrieval based framework that provides the most likely value for an attribute. Our proposed method is capable of addressing variable length passage sizes and different validation criteria for the extracted values corresponding to each attribute to be found. We evaluate our approach by constructing a manually annotated ground-truth from a set of 50 research papers with reported studies on smoking cessation. Wellcome Trust

Rapid cancer cell proliferation promotes the production of reducing equivalents, which counteract the effects of relatively high levels of reactive oxygen species (ROS). ROS levels increase in response to chemotherapy and cell death while an increase in antioxidant capacity can confer resistance to chemotherapy and is associated with an aggressive tumor phenotype. The pentose phosphate pathway (PPP) is a major site of NADPH production in the cell, which is used to maintain the main intracellular antioxidant, glutathione, in its reduced state. Previous studies have shown that the rate of hyperpolarized [1-$^{13}$C]dehydroascorbic acid (DHA) reduction, which can be measured $\textit{in vivo}$ using non-invasive $^{13}$C magnetic resonance spectroscopic imaging, is increased in tumors and that this is correlated with the levels of reduced glutathione. We show here that the rate of hyperpolarized [1-$^{13}$C]DHA reduction is increased in tumors that have been oxidatively pre-stressed by depleting the glutathione pool by buthionine sulfoximine treatment. This increase was associated with a corresponding increase in PPP flux, assessed using $^{13}$C-labeled glucose, and an increase in glutaredoxin activity, which catalyzes the glutathione-dependent reduction of DHA. These results show that the rate of DHA reduction does not depend only on the level of reduced glutathione, but also on the rate of NADPH production, contradicting the conclusions of some previous studies. Hyperpolarized [1-$^{13}$C]DHA can be used therefore to assess the capacity of tumor cells to resist oxidative stress in vivo. However, DHA administration resulted in transient respiratory arrest and cardiac depression, which may prevent translation to the clinic.

A contribution to PAGES' PALSEA2 working group. ABSTRACT : We use relative sea level (RSL) reconstructions and a spatiotemporal statistical model to estimate the rate of uplift of the Cape Fear Arch a Mesozoic structural high during the last ~4000 years. We reconstructed RSL using 12 radiocarbon dated samples of basal salt marsh sediment preserved at Elizabeth Creek Marsh on the Cape Fear River. The new data show that RSL rose by ~3?m during the past ~4.6 ka at an average rate of 0.67?±?0.12?mm a-1. RSL reconstructions from other sites in southern North Carolina (which have rates of 0.91?±?0.10 to 0.84?±?0.24?mm a-1) probably show (P?>?0.9) higher rates of regional RSL rise for the same period while sites from northern South Carolina (which have rates of 0.72?±?0.17 to 0.80?±?0.21?mm a-1) probably (P?>?0.67) show the same. We attribute the differences between Elizabeth Creek Marsh and neighboring regions to uplift of the Cape Fear Arch which we estimate to be 0.24?±?0.15?mm a-1. Uplift of the arch may be responsible for lower rates of 20th century RSL rise recorded by the Wilmington tide gauge relative to rates measured elsewhere along the US mid Atlantic coast.

In this study non-negative matrix factorization (NMF) was hierarchically applied to simulated and in vivo three-dimensional 3 T MRSI data of the prostate to extract patterns for tumour and benign tissue and to visualize their spatial distribution. Our studies show that the hierarchical scheme provides more reliable tissue patterns than those obtained by performing only one NMF level. We compared the performance of three different NMF implementations in terms of pattern detection accuracy and efficiency when embedded into the same kind of hierarchical scheme. The simulation and in vivo results show that the three implementations perform similarly, although one of them is more robust and better pinpoints the most aggressive tumour voxel(s) in the dataset. Furthermore, they are able to detect tumour and benign tissue patterns even in spectra with lipid artefacts. Copyright © 2016 John Wiley & Sons, Ltd. ispartof: Nmr In Biomedicine vol:29 issue:6 pages:751-758 ispartof: location:England status: published

niet beschikbaar

The fluoroquinolones are a new class of antimicrobial agents structurally related to nalidixic acid. They have a broad spectrum of activity against pathogens, including Pseudomonas aeruginosa, other multiresistant gram-negative bacteria, and methicillin-resistant Staphylococcus aureus but not anaerobes. They are well absorbed after oral administration, and some achieve serum and tissue levels well exceeding the minimal inhibitory concentrations for susceptible bacteria. Adverse reactions are rare, and when they occur they are usually mild. Use of quinolones should be avoided in children because of possible damage to developing cartilage. These agents should prove useful in the treatment of urinary tract infections caused by bacteria resistant to other oral agents, bacterial gastroenteritis, and gonococcal infections. The use of quinolones may potentially reduce the cost of treatment of certain systemic infections caused by multiantimicrobial resistant organisms because outpatient oral therapy is possible.

$\textbf{Purpose:}$ Dynamic magnetic resonance spectroscopic imaging of hyperpolarized $^{13}$C-labeled cell substrates has enabled the investigation of tissue metabolism in vivo. Currently observation of these hyperpolarized substrates is limited mainly to $^{13}$C detection. We describe here an imaging pulse sequence that enables proton observation by using polarization transfer from the hyperpolarized $^{13}$C nucleus to spin-coupled protons. $\textbf{Methods:}$ The pulse sequence transfers $^{13}$C hyperpolarization to $^1$H using a modified reverse insensitive nuclei enhanced by polarization transfer (INEPT) sequence that acquires a fully refocused echo. The resulting hyperpolarized $^1$H signal is acquired using a 2D echo-planar trajectory. The efficiency of polarization transfer was investigated using simulations with and without T$_1$ and T$_2$ relaxation of both the $^1$H and $^{13}$C nuclei. $\textbf{Results:}$ Simulations showed that $^1$H detection of the hyperpolarized $^{13}$C nucleus in lactate should increase significantly the signal-to-noise ratio when compared with direct $^{13}$C detection at 3T. However the advantage of $^1$H detection is expected to disappear at higher fields. Dynamic $^1$H images of hyperpolarized [1-$^{13}$C]lactate, with a spatial resolution of 1.25 × 1.25 mm$^2$, were acquired from a phantom injected with hyperpolarized [1-$^{13}$C]lactate and from tumors in vivo following injection of hyperpolarized [1-$^{13}$C]pyruvate. $\textbf{Conclusions:}$ The sequence allows $^1$H imaging of hyperpolarized $^{13}$C-labeled substrates in vivo.

Rapid cancer cell proliferation promotes the production of reducing equivalents, which counteract the effects of relatively high levels of reactive oxygen species (ROS). ROS levels increase in response to chemotherapy and cell death while an increase in antioxidant capacity can confer resistance to chemotherapy and is associated with an aggressive tumor phenotype. The pentose phosphate pathway (PPP) is a major site of NADPH production in the cell, which is used to maintain the main intracellular antioxidant, glutathione, in its reduced state. Previous studies have shown that the rate of hyperpolarized [1-$^{13}$C]dehydroascorbic acid (DHA) reduction, which can be measured $\textit{in vivo}$ using non-invasive $^{13}$C magnetic resonance spectroscopic imaging, is increased in tumors and that this is correlated with the levels of reduced glutathione. We show here that the rate of hyperpolarized [1-$^{13}$C]DHA reduction is increased in tumors that have been oxidatively pre-stressed by depleting the glutathione pool by buthionine sulfoximine treatment. This increase was associated with a corresponding increase in PPP flux, assessed using $^{13}$C-labeled glucose, and an increase in glutaredoxin activity, which catalyzes the glutathione-dependent reduction of DHA. These results show that the rate of DHA reduction does not depend only on the level of reduced glutathione, but also on the rate of NADPH production, contradicting the conclusions of some previous studies. Hyperpolarized [1-$^{13}$C]DHA can be used therefore to assess the capacity of tumor cells to resist oxidative stress in vivo. However, DHA administration resulted in transient respiratory arrest and cardiac depression, which may prevent translation to the clinic.

Summary PIK3CA, encoding the PI3Kα isoform, is the most frequently mutated oncogene in estrogen receptor (ER)-positive breast cancer. Isoform-selective PI3K inhibitors are used clinically but intrinsic and acquired resistance limits their utility. Improved selection of patients that will benefit from these drugs requires predictive biomarkers. We show here that persistent FOXM1 expression following drug treatment is a biomarker of resistance to PI3Kα inhibition in ER+ breast cancer. FOXM1 drives expression of lactate dehydrogenase (LDH) but not hexokinase 2 (HK-II). The downstream metabolic changes can therefore be detected using MRI of LDH-catalyzed hyperpolarized 13C label exchange between pyruvate and lactate but not by positron emission tomography measurements of HK-II-mediated trapping of the glucose analog 2-deoxy-2-[18F]fluorodeoxyglucose. Rapid assessment of treatment response in breast cancer using this imaging method could help identify patients that benefit from PI3Kα inhibition and design drug combinations to counteract the emergence of resistance., Graphical Abstract, Highlights • Imaging hyperpolarized [1-13C]pyruvate metabolism detects response to PI3Kα inhibitors • PI3Kα inhibitors downregulate FOXM1 expression in ER+ breast tumor models • FOXM1 induces LDH expression and 13C label exchange between pyruvate and lactate • Imaging [1-13C]pyruvate metabolism could be used clinically to guide treatment, Ros et al. find that imaging of hyperpolarized [1-13C]pyruvate metabolism allows early detection of response and resistance to PI3Kα inhibition in PIK3CA-mutant ER+ breast cancer, which could be used clinically to guide treatment. Increased expression of FOXM1 results in resistance to PI3Kα inhibition and sustains LDH expression.