"Earth worm wit lies under ground": The compositional genesis of Coleridge's "limbo" constellation

This is the final version. It was first published by University of Chicago Press and the original publication can now be accessed at http://www.jstor.org/stable/10.1086/670161?origin=JSTOR-pdf

High-entropy alloys: a critical assessment of their founding principles and future prospects

High-entropy alloys (HEAs) are a relatively new class of materials that have gained considerable attention from the metallurgical research community over recent years. They are characterised by their unconventional compositions, in that they are not based around a single major component, but rather comprise multiple principal alloying elements. Four core effects have been proposed in HEAs: (1) the entropic stabilisation of solid solutions, (2) the severe distortion of their lattices, (3) sluggish diffusion kinetics and (4) that properties are derived from a cocktail effect. By assessing these claims on the basis of existing experimental evidence in the literature, as well as classical metallurgical understanding, it is concluded that the significance of these effects may not be as great as initially believed. The effect of entropic stabilisation does not appear to be overarching, insufficient evidence exists to establish the strain in the lattices of HEAs, and rapid precipitation observed in some HEAs suggests their diffusion kinetics are not necessarily anomalously slow in comparison to conventional alloys. The meaning and influence of the cocktail effect is also a matter for debate. Nevertheless, it is clear that HEAs represent a stimulating opportunity for the metallurgical research community. The complex nature of their compositions means that the discovery of alloys with unusual and attractive properties is inevitable. It is suggested that future activity regarding these alloys seeks to establish the nature of their physical metallurgy, and develop them for practical applications. Their use as structural materials is one of the most promising and exciting opportunities. To realise this ambition, methods to rapidly predict phase equilibria and select suitable HEA compositions are needed, and this constitutes a significant challenge. However, while this obstacle might be considerable, the rewards associated with its conquest are even more substantial. Similarly, the challenges associated with comprehending the behaviour of alloys with complex compositions are great, but the potential to enhance our fundamental metallurgical understanding is more remarkable. Consequently, HEAs represent one of the most stimulating and promising research fields in materials science at present.One of the authors (NGJ) would like to acknowledge the EPSRC/Rolls-Royce Strategic Partnership for funding under EP/M005607/1

Fine-scale precipitation in the high-entropy alloy Al<inf>0.5</inf>CrFeCoNiCu

The high-entropy alloy Al0:5CrFeCoNiCu has been shown to consist of two stable, face-centred cubic solid solutions at temperatures approaching its solidus; one rich in Cr, Fe, Co & Ni (dendritic) and the other rich in Cu (interdendritic). Whilst some studies have suggested that the high-temperature microstructure may be metastably retained to room temperature through rapid cooling, evidence of phase decomposition has also been reported. In this study, fine-scale precipitation has been observed in samples of Al0:5CrFeCoNiCu that have been rapidly cooled after casting, and water quenched following ageing for 1000 h at 1000°C. Contrary to previous reports, in the as-cast state, the two face- centred cubic phases, as well as an L12 phase, were found in both dendritic and interdendritic areas, with the dendritic areas having undergone a spinodal decomposition. After ageing and quenching, L12 precipitates were found in both dendritic and interdendritic areas, and precipitates of the Cr-, Fe-, Co- and Ni-enriched face-centred cubic phase were found in the Cu-rich interdendritic regions. Given the nature of the heat treatments applied, the results suggest that precipitation in the alloy is rapid and cannot be avoided, even when the material is cooled quickly to room temperature.The authors acknowledge funding from Rolls-Royce plc and the EPSRC under the Rolls-Royce/EPSRC Strategic Partnership (EP/H022309/1).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.msea.2015.08.01

Development and implementation of a decision pathway for general practitioners for the management or referral of suspected allergy.

Many patients with suspected allergy are referred to specialist care inappropriately. We aimed to develop and implement an online decision pathway to aid General Practitioners' (GPs) management decisions in suspected allergy. Our study involved 1487 GPs, 3 referral management centres, 5 GP system suppliers, 4 primary care trusts, and 1 specialist allergy clinic. The pathway was implemented by 3/5 GP system suppliers, published to Map of Medicine and on a specialist clinic website. In the first year, the pathway ranked in the top 10/160 local care maps accessed via Map of Medicine and was viewed 900 times. Only 96 GPs registered to use the clinic website. Only 110 (7%) GPs responded to the feedback request, of which 13/110 (12%) had used the pathway; nearly all thought it useful. It was used by referral management centres as explanation of rejected referrals. Alternative approaches to embed its use are required. Significance for public healthOne in three people in the UK are affected by allergies during their lifetime. Early diagnosis and appropriate management can improve quality of life and reduce emergency hospitalisation. However, referring patients to secondary care is costly in terms of time and resources. We developed a pathway algorithm to support General Practitioners' (GPs) allergy management and referral decisions to ensure that all referrals to specialist clinics were appropriate. The study illustrates a real world implementation with lessons for those seeking to improve the primary-secondary care interface, implementing pathways in various formats. In the UK, Map of Medicine seems to be the most used software. We demonstrated the difficulty of reaching GPs to encourage adoption of online decision support and suggest new ways forward by expanding care pathways into more detailed protocols for use directly by patients

Systemic Therapy for Hereditary Breast Cancers.

Approximately 5% to 10% of all breast cancers are hereditary; many of which are caused by pathogenic variants in genes required for homologous recombination, including BRCA1 and BRCA2. Here we discuss systemic treatment for such breast cancers, including approved chemotherapeutic approaches and also targeted treatment approaches using poly-(ADP ribose) polymerase inhibitors. We also discuss experimental approaches to treating hereditary breast cancer, including new small molecule DNA repair inhibitors and also immunomodulatory agents. Finally, we discuss how drug resistance emerges in patients with hereditary breast cancer, how this might be delayed or prevented, and how biomarker-adapted treatment is molding the future management of hereditary breast cancer

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

The Moderating Role of Parental Sleep Knowledge on Children with Developmental Disabilities and Their Parents’ Sleep

Background: Children with intellectual and developmental difficulties often experience sleep problems, which in turn may impact parental sleep patterns. This study explored the role of parental sleep knowledge as a moderator on the relationship between child sleep and parental sleep impairment. Methods: 582 parents or caregivers (92.6% mothers) of children with different developmental disabilities (Age M = 9.34, 29.5% females) such as Down’s syndrome, participated in an online survey. Multiple regression analysis was conducted. Results: Parental sleep knowledge of child sleep was a moderating variable in the relationship between child sleep nocturnal duration and parental sleep impairment. Although overall, sleep knowledge was high in this sample, two specific knowledge gaps were identified namely child sleep duration requirements, and the recognition of signs of a well-rested child. Conclusion: This study has provided evidence that increased parental sleep knowledge can positively impact both child and parental sleep outcomes

Plasma REST: A novel candidate biomarker of Alzheimer\u27s 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

Reducing radiation in chronic total occlusion percutaneous coronary interventions.

The field of percutaneous intervention for chronic total occlusion (CTO) has enjoyed significant innovations in the recent years. Novel techniques and technologies have revolutionized the field and have resulted in considerably higher success rates even in patients with high anatomical complexity. Successful CTO recanalization is associated with significant clinical benefits, such as the improvement of angina and quality of life, reduced rates of surgical revascularization, improvement of left ventricular function and decreased mortality rates. However, complex CTO procedures often require prolonged x-ray exposure which have been associated with adverse long term outcomes