Magnetically soft, high moment grain-refined Fe films: application to magnetic tunnel junctions

The effect of N-doping on the microstructure and magnetic properties of thin Fe layers has been employed to construct all Fe-electrode magnetic tunnel junctions that displayed the tunneling magnetoresistance (TMR) effect. Using low nitrogen doses, a reduction in coercivity was achieved due to grain refinement, without a concurrent decrease in the saturation magnetization of the Fe films caused by the formation of crystalline iron nitride phases. It was demonstrated that this N-induced grain refinement can be applied beneficially to control the switching field of the "free" layer in magnetic trilayer structures. In general the ability to control magnetic softness without reducing saturation magnetization will prove important for incorporating high spin-polarized materials into spin valves and TMR devices

Monitoring and improving the quality of person-centred care in health and social settings using Dementia Care Mapping (DCM): Staff experiences of implementation barriers and supports

Dementia Care Mapping (DCM) is a person-centred care quality monitoring and improvement tool used for nearly 20 years in formal dementia care settings and there are thousands of people trained in its use internationally. However, little is known about if and how DCM is used in practice or regarding application of inter-rater reliability checks to ensure data quality. This study aimed to explore the application of DCM in practice in the UK. A mixed methods design including an on-line survey and in-depth, semi-structured interviews was employed. There were 98 survey respondents, representing 71 health and social care, University/research and training/consultancy organisations. Twenty-one people participated in the semi-structured interviews. Fifty-nine percent of survey respondents had used DCM since completing training. Those working in clinical roles and in health and social care provider organisations were least likely to have used DCM. A range of barriers and supports to use of DCM in practice after training were reported, including lack of management support and time. The majority of those who had used DCM also conducted inter-rater reliability checks at least once per year or more frequently. Of the 20% who did not the main barriers to this were absence of someone to conduct the checks with and lack of time and resources. The study has shown that it is possible to apply an evidence-based quality monitoring and improvement tool such as DCM to support implementation of person-centred care in practice, despite widespread limitations on time and resources as well as identifying a range of setting conditions that can help or hinder implementation

Health information needs, source preferences and engagement behaviours of women with metastatic breast cancer across the care continuum: protocol for a scoping review

INTRODUCTION: The health information needs, information source preferences and engagement behaviours of women with metastatic breast cancer (mBC) depend on personal characteristics such as education level, prior knowledge, clinical complications, comorbidities and where they are in the cancer journey. A thorough understanding of the information behaviours of women living with mBC is essential to the provision of optimal care. A preliminary literature review suggests that there is little research on this topic, but that there may be lessons from a slightly broader literature. This review will identify what is known and what is not known about the health information needs, acquisition and influences of women with mBC across the care continuum. Findings will help to identify research needs and specific areas where in-depth systematic reviews may be feasible, as well as inform evidence-based interventions to address the health information needs of female patients with mBC with different demographics and characteristics and across the mBC journey. METHODS AND ANALYSIS: A scoping review will be performed using the guidelines of Arksey and O'Malley as updated by subsequent authors to systematically search scientific and grey literature for articles in English that discuss the health information needs, source preferences, engagement styles, and associated personal and medical attributes of women ≥18 years living with mBC at different stages of the disease course. A variety of databases (including Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, Excerpta Medica Database (EMBASE), Academic Search Premier, Cochrane Database of Systematic Reviews, PsycINFO, Health Source: Nursing/Academic Edition, and PQDT Open), oncology, patient advocacy and governmental websites will be searched from inception to present day. Research and non-research literature will be included; no study designs will be excluded. The six-stage Arksey and O'Malley scoping review methodological framework involves: (1) identifying the research question; (2) searching for relevant studies; (3) selecting studies; (4) charting the data; (5) collating, summarising and reporting the results; and (6) consulting with stakeholders to inform or validate study findings (optional). Data will be extracted and analysed using a thematic chart and descriptive content analysis. ETHICS AND DISSEMINATION: Being a secondary analysis, this research will not require ethics approval. Results will be disseminated through patient support organisations and websites and publications targeting healthcare professionals, advocates and patients

White matter lesions characterise brain involvement in moderate to severe chronic obstructive pulmonary disease, but cerebral atrophy does not.

BACKGROUND: Brain pathology is relatively unexplored in chronic obstructive pulmonary disease (COPD). This study is a comprehensive investigation of grey matter (GM) and white matter (WM) changes and how these relate to disease severity and cognitive function. METHODS: T1-weighted and fluid-attenuated inversion recovery images were acquired for 31 stable COPD patients (FEV1 52.1% pred., PaO2 10.1 kPa) and 24 age, gender-matched controls. T1-weighted images were segmented into GM, WM and cerebrospinal fluid (CSF) tissue classes using a semi-automated procedure optimised for use with this cohort. This procedure allows, cohort-specific anatomical features to be captured, white matter lesions (WMLs) to be identified and includes a tissue repair step to correct for misclassification caused by WMLs. Tissue volumes and cortical thickness were calculated from the resulting segmentations. Additionally, a fully-automated pipeline was used to calculate localised cortical surface and gyrification. WM and GM tissue volumes, the tissue volume ratio (indicator of atrophy), average cortical thickness, and the number, size, and volume of white matter lesions (WMLs) were analysed across the whole-brain and regionally - for each anatomical lobe and the deep-GM. The hippocampus was investigated as a region-of-interest. Localised (voxel-wise and vertex-wise) variations in cortical gyrification, GM density and cortical thickness, were also investigated. Statistical models controlling for age and gender were used to test for between-group differences and within-group correlations. Robust statistical approaches ensured the family-wise error rate was controlled in regional and local analyses. RESULTS: There were no significant differences in global, regional, or local measures of GM between patients and controls, however, patients had an increased volume (p = 0.02) and size (p = 0.04) of WMLs. In patients, greater normalised hippocampal volume positively correlated with exacerbation frequency (p = 0.04), and greater WML volume was associated with worse episodic memory (p = 0.05). A negative relationship between WML and FEV1 % pred. approached significance (p = 0.06). CONCLUSIONS: There was no evidence of cerebral atrophy within this cohort of stable COPD patients, with moderate airflow obstruction. However, there were indications of WM damage consistent with an ischaemic pathology. It cannot be concluded whether this represents a specific COPD, or smoking-related, effect

Quasi-diffusion magnetic resonance imaging (QDI): A fast, high b-value diffusion imaging technique.

To enable application of non-Gaussian diffusion magnetic resonance imaging (dMRI) techniques in large-scale clinical trials and facilitate translation to clinical practice there is a requirement for fast, high contrast, techniques that are sensitive to changes in tissue structure which provide diagnostic signatures at the early stages of disease. Here we describe a new way to compress the acquisition of multi-shell b-value diffusion data, Quasi-Diffusion MRI (QDI), which provides a probe of subvoxel tissue complexity using short acquisition times (1-4 min). We also describe a coherent framework for multi-directional diffusion gradient acquisition and data processing that allows computation of rotationally invariant quasi-diffusion tensor imaging (QDTI) maps. QDI is a quantitative technique that is based on a special case of the Continuous Time Random Walk model of diffusion dynamics and assumes the presence of non-Gaussian diffusion properties within tissue microstructure. QDI parameterises the diffusion signal attenuation according to the rate of decay (i.e. diffusion coefficient, D in mm2 s-1) and the shape of the power law tail (i.e. the fractional exponent, α). QDI provides analogous tissue contrast to Diffusional Kurtosis Imaging (DKI) by calculation of normalised entropy of the parameterised diffusion signal decay curve, Hn, but does so without the limitations of a maximum b-value. We show that QDI generates images with superior tissue contrast to conventional diffusion imaging within clinically acceptable acquisition times of between 84 and 228 s. We show that QDI provides clinically meaningful images in cerebral small vessel disease and brain tumour case studies. Our initial findings suggest that QDI may be added to routine conventional dMRI acquisitions allowing simple application in clinical trials and translation to the clinical arena

DNMTs are required for delayed genome instability caused by radiation

This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited - Copyright @ 2012 Landes Bioscience.The ability of ionizing radiation to initiate genomic instability has been harnessed in the clinic where the localized delivery of controlled doses of radiation is used to induce cell death in tumor cells. Though very effective as a therapy, tumor relapse can occur in vivo and its appearance has been attributed to the radio-resistance of cells with stem cell-like features. The molecular mechanisms underlying these phenomena are unclear but there is evidence suggesting an inverse correlation between radiation-induced genomic instability and global hypomethylation. To further investigate the relationship between DNA hypomethylation, radiosensitivity and genomic stability in stem-like cells we have studied mouse embryonic stem cells containing differing levels of DNA methylation due to the presence or absence of DNA methyltransferases. Unexpectedly, we found that global levels of methylation do not determine radiosensitivity. In particular, radiation-induced delayed genomic instability was observed at the Hprt gene locus only in wild-type cells. Furthermore, absence of Dnmt1 resulted in a 10-fold increase in de novo Hprt mutation rate, which was unaltered by radiation. Our data indicate that functional DNMTs are required for radiation-induced genomic instability, and that individual DNMTs play distinct roles in genome stability. We propose that DNMTS may contribute to the acquirement of radio-resistance in stem-like cells.This study is funded by NOTE, BBSRC and the Royal Society Dorothy Hodgkin Research Fellowship

On the linear fractional self-attracting diffusion

In this paper, we introduce the linear fractional self-attracting diffusion driven by a fractional Brownian motion with Hurst index 1/2<H<1, which is analogous to the linear self-attracting diffusion. For 1-dimensional process we study its convergence and the corresponding weighted local time. For 2-dimensional process, as a related problem, we show that the renormalized self-intersection local time exists in L^2 if $\frac12<H<\frac3{4}$.Comment: 14 Pages. To appear in Journal of Theoretical Probabilit

Disruption of white matter connectivity in chronic obstructive pulmonary disease.

BACKGROUND: Mild cognitive impairment is a common systemic manifestation of chronic obstructive pulmonary disease (COPD). However, its pathophysiological origins are not understood. Since, cognitive function relies on efficient communication between distributed cortical and subcortical regions, we investigated whether people with COPD have disruption in white matter connectivity. METHODS: Structural networks were constructed for 30 COPD patients (aged 54-84 years, 57% male, FEV1 52.5% pred.) and 23 controls (aged 51-81 years, 48% Male). Networks comprised 90 grey matter regions (nodes) interconnected by white mater fibre tracts traced using deterministic tractography (edges). Edges were weighted by the number of streamlines adjusted for a) streamline length and b) end-node volume. White matter connectivity was quantified using global and nodal graph metrics which characterised the networks connection density, connection strength, segregation, integration, nodal influence and small-worldness. Between-group differences in white matter connectivity and within-group associations with cognitive function and disease severity were tested. RESULTS: COPD patients' brain networks had significantly lower global connection strength (p = 0.03) and connection density (p = 0.04). There was a trend towards COPD patients having a reduction in nodal connection density and connection strength across the majority of network nodes but this only reached significance for connection density in the right superior temporal gyrus (p = 0.02) and did not survive correction for end-node volume. There were no other significant global or nodal network differences or within-group associations with disease severity or cognitive function. CONCLUSION: COPD brain networks show evidence of damage compared to controls with a reduced number and strength of connections. This loss of connectivity was not sufficient to disrupt the overall efficiency of network organisation, suggesting that it has redundant capacity that makes it resilient to damage, which may explain why cognitive dysfunction is not severe. This might also explain why no direct relationships could be found with cognitive measures. Smoking and hypertension are known to have deleterious effects on the brain. These confounding effects could not be excluded

Plasma REST: a novel candidate biomarker of Alzheimer's disease is modified by psychological intervention in an at-risk population.

The repressor element 1-silencing transcription (REST) factor is a key regulator of the aging brain's stress response. It is reduced in conditions of stress and Alzheimer's disease (AD), which suggests that increasing REST may be neuroprotective. REST can be measured peripherally in blood plasma. Our study aimed to (1) examine plasma REST levels in relation to clinical and biological markers of neurodegeneration and (2) alter plasma REST levels through a stress-reduction intervention-mindfulness training. In study 1, REST levels were compared across the following four well-characterized groups: healthy elderly (n=65), mild cognitive impairment who remained stable (stable MCI, n=36), MCI who later converted to dementia (converter MCI, n=29) and AD (n=65) from the AddNeuroMed cohort. REST levels declined with increasing severity of risk and impairment (healthy elderly&gt;stable MCI&gt;converter MCI&gt;AD, F=6.35, P&lt;0.001). REST levels were also positively associated with magnetic resonance imaging-based hippocampal and entorhinal atrophy and other putative blood-based biomarkers of AD (Ps&lt;0.05). In study 2, REST was measured in 81 older adults with psychiatric risk factors for AD before and after a mindfulness-based stress reduction intervention or an education-based placebo intervention. Mindfulness-based training caused an increase in REST compared with the placebo intervention (F=8.57, P=0.006), and increased REST was associated with a reduction in psychiatric symptoms associated with stress and AD risk (Ps&lt;0.02). Our data confirm plasma REST associations with clinical severity and neurodegeneration, and originally, that REST is modifiable by a psychological intervention with clinical benefit