Solid-State NMR Studies of Ternary Alloys for use in Sodium-ion Batteries

Due to the pressures of climate change it is important to produce methods of renewable energy generation and storage which are cheap and can be applied to many industries and consumer needs. Sodium-ion batteries have proved viable alternatives to current Li-ion batteries, however they are unusable with graphite, which is the best negative electrode material we currently use. It is therefore important to develop other negative electrode materials which can perform to the same standards. This research aims to investigate the performance of TiSnSb, a conversion negative electrode material, against sodium using electro-cycling and Solid-state Magic Angle Spinning Nuclear Magnetic Resonance (MAS ssNMR) to elucidate the chemical reactions which take place within the battery cells. Battery cells were constructed in a glovebox under an argon atmosphere, and data was obtained using a benchtop potentiostat and a Bruker 500. Data was obtained for TiSnSb at C/2 and 4C rates for the first sodiation (discharge), first de-sodiation (charge), and second de-sodiation. C rate is defined as the number of sodium ions inserted per formula unit of TiSnSb per hour. Data was also collected for a rough mixture of Ti+Sn+Sb. TiSnSb was found to operate via a conversion mechanism upon sodiation and de-sodiation with starting potentials of 2.6 – 2.8 V achieved consistently for multiple electrodes. In contrast Ti+Sn+Sb operates through an alloying reaction with multiple ‘stages’ of the reaction. The electrochemical rate has a strong effect on the number of Na ions inserted into the structure and the phases formed as evident from the potential profiles and MAS NMR spectra

M̀oral sense' from the Cambridge platonists to Adam Smith

This thesis traces the development of the notion of 'moral sense' from the midseventeenth century to the mid-eighteenth century. Its roots are in the moral writings of some of the Cambridge Platonists, it flourished as a moral theory with Francis Hutcheson in the 1720s, and it had many supporters in the decades that followed. Only with the much more astute philosophies of David Hume and Adam Smith were the basic presumptions behind the notion of a natural moral sense examined with renewed care. David Hume, I argue, retains the veneer of a moral sense theory, while providing arguments able to challenge it severely. Only with Adam Smith, in his Theory of Moral Sentiments of 1759, is there a direct criticism and rejection of the moral sense theory in the form that it had held since the third Earl of Shaftesbury and Hutcheson. One of the important assessments of this period in the history of British moral philosophy, David Norton's From Moral Sense to Common-Sense: An Essay on the Development of Scottish Common Sense Philosophy of 1966 (revised as David Hume: Common-Sense Moralist, Sceptical Metaphysician), made no room for Adam Smith's epistemological criticisms, nor his retention of some of the elements of the theory that he was so disparaging about. After an introductory chapter, chapter two surveys some of the moral writings of the Cambridge Platonists, especially Benjamin Whichcote and Henry More. An unmovable belief in God's goodness and his beneficence towards mankind was evidence that the human natural faculties included a moral faculty as its crown. Its proper use meant that people spontaneously and correctly could apprehend moral qualities in peoples actions and character traits. This 'boniform faculty' was happily confused, in their writings, with a bias towards benevolence and this confusion is still to be found in Hutcheson. The notion of the moral sense was consolidated by Anthony Ashley Cooper, the third Earl of Shaftesbury. He is considered in chapter three. His Characteristics of Men, Manners, Opinions, Times disseminated this optimistic assessment of human nature, underpinned by appeal to a natural moral faculty of moral discernment and motivation. Only with Francis Hutcheson was the notion of a moral sense self-consciously expounded as a theory. In chapter four I deal with the epistemology of Hutcheson's account of the moral sense, looking at the details of how Hutcheson describes the activity of the moral sense, either as a faculty of sense, or as a sensibility. In chapter five I suggest that his moral-sense theory is supplemented by a virtue theory. The direct objects of the moral sense are the virtues and vices, but Hutcheson's interest in developing what he sees as an adequate epistemology never makes him lose sight of his goal to exhort people to live well and cultivate virtue. Chapter six surveys some other moral-sense writers. Notable among them is Joseph Butler. His discussion of conscience in his Fifteen Sermons from Rolls Chapel is well within the moral sense tradition. Chapter seven considers the moral sense aspects of David Hume' s moral writings. His fundamental reassessment of human nature still leaves a place for some of the terminology of the moral sense, as well as a new emphasis on the non-moral assessment of others by 'sympathy'. It is left to Smith, however, to challenge explicitly some of the arguments brought to defend the belief in a moral sense. This is the burden of chapter eight. Smith leaves no doubt as to the flimsiness of this philosophical construction. Yet, in tearing it down, he retains two very important notions. The first is a secure, if more cautious, role for the emotions in our moral assessment of others. The second is to secure the impartial spectator as the personification of ideal moral standards to be aspired to. A short conclusion follows

Initial Metabolic Profiles Are Associated with 7-Day Survival among Infants Born at 22-25 Weeks of Gestation.

OBJECTIVE:To evaluate the association between early metabolic profiles combined with infant characteristics and survival past 7 days of age in infants born at 22-25 weeks of gestation. STUDY DESIGN:This nested case-control consisted of 465 singleton live births in California from 2005 to 2011 at 22-25 weeks of gestation. All infants had newborn metabolic screening data available. Data included linked birth certificate and mother and infant hospital discharge records. Mortality was derived from linked death certificates and death discharge information. Each death within 7 days was matched to 4 surviving controls by gestational age and birth weight z score category, leaving 93 cases and 372 controls. The association between explanatory variables and 7-day survival was modeled via stepwise logistic regression. Infant characteristics, 42 metabolites, and 12 metabolite ratios were considered for model inclusion. Model performance was assessed via area under the curve. RESULTS:The final model included 1 characteristic and 11 metabolites. The model demonstrated a strong association between metabolic patterns and infant survival (area under the curve [AUC] 0.885, 95% CI 0.851-0.920). Furthermore, a model with just the selected metabolites performed better (AUC 0.879, 95% CI 0.841-0.916) than a model with multiple clinical characteristics (AUC 0.685, 95% CI 0.627-0.742). CONCLUSIONS:Use of metabolomics significantly strengthens the association with 7-day survival in infants born extremely premature. Physicians may be able to use metabolic profiles at birth to refine mortality risks and inform postnatal counseling for infants born at <26 weeks of gestation

The COMET (Comparison of Operative versus Monitoring and Endocrine Therapy) trial: a phase III randomised controlled clinical trial for low-risk ductal carcinoma in situ (DCIS)

Introduction Ductal carcinoma in situ (DCIS) is a noninvasive non-obligate precursor of invasive breast cancer. With guideline concordant care (GCC), DCIS outcomes are at least as favourable as some other early stage cancer types such as prostate cancer, for which active surveillance (AS) is a standard of care option. However, AS has not yet been tested in relation to DCIS. The goal of the COMET (Comparison of Operative versus Monitoring and Endocrine Therapy) trial for low-risk DCIS is to gather evidence to help future patients consider the range of treatment choices for low-risk DCIS, from standard therapies to AS. The trial will determine whether there may be some women who do not substantially benefit from current GCC and who could thus be safely managed with AS. This protocol is version 5 (11 July 2018). Any future protocol amendments will be submitted to Quorum Centralised Institutional Review Board/local institutional review boards for approval via the sponsor of the study (Alliance Foundation Trials). Methods and analysis COMET is a phase III, randomised controlled clinical trial for patients with low-risk DCIS. The primary outcome is ipsilateral invasive breast cancer rate in women undergoing GCC compared with AS. Secondary objectives will be to compare surgical, oncological and patient-reported outcomes. Patients randomised to the GCC group will undergo surgery as well as radiotherapy when appropriate; those in the AS group will be monitored closely with surgery only on identification of invasive breast cancer. Patients in both the GCC and AS groups will have the option of endocrine therapy. The total planned accrual goal is 1200 patients. Ethics and dissemination The COMET trial will be subject to biannual formal review at the Alliance Foundation Data Safety Monitoring Board meetings. Interim analyses for futility/safety will be completed annually, with reporting following Consolidated Standards of Reporting Trials (CONSORT) guidelines for noninferiority trials

“I expect it as part of the kind of package deal when you sign up to these things” - Motivations and Experiences of Ghosting

Most online dating users perceive ghosting to be common and expect that there is a chance of being ghosted on online dating platforms (ODPs). The current study extends previous research by gaining qualitative insight into what people believe constitutes ghosting behaviour, why people ghost, and how ghosting makes them feel. This study aimed to 1) explore individuals' motivations to ghost, 2) explore individuals experiences of ghosting and 3) gather the ghosters views of ghosting definition. A total of 12 online interviews were conducted. All participants had previously ghosted on ODPs and lived in the UK. Data was analysed using reflective thematic analysis. The presented five themes reflect a contextual realist approach, using both semantic and latent coding, and reveal that ghosting is considered the norm on ODP. There are general and specific motivations underpinning ghosting behaviour, producing a mixed emotional response from the ghoster. The findings also shed light on how we can better define ghosting, with participants having concerns with the word relationship. Finally, we highlight several protective factors that can minimise the likelihood of ghosting. Based on our findings we suggest that ghosting be defined as being a gradual or sudden one sided ceasing of communication to end the progress of an interaction with another person. While we found several protective factors that can minimise the likelihood of ghosting, these are unique to the individual and ghosting cannot be abolished as it has become a normative and embedded practice within ODP

Early on-treatment transcriptional profiling as a tool for improving pathological response prediction in HER2-positive inflammatory breast cancer

Background: Inflammatory breast cancer (IBC) is a rare and understudied disease, with 40% of cases presenting with human epidermal growth factor receptor 2 (HER2)-positive subtype. The goals of this study were to (i) assess the pathologic complete response (pCR) rate of short-term neoadjuvant dual-HER2-blockade and paclitaxel, (ii) contrast baseline and on-treatment transcriptional profiles of IBC tumor biopsies associated with pCR, and (iii) identify biological pathways that may explain the effect of neoadjuvant therapy on tumor response. Patients and Methods: A single-arm phase II trial of neoadjuvant trastuzumab (H), pertuzumab (P), and paclitaxel for 16 weeks was completed among patients with newly diagnosed HER2-positive IBC. Fresh-frozen tumor biopsies were obtained pretreatment (D1) and 8 days later (D8), following a single dose of HP, prior to adding paclitaxel. We performed RNA-sequencing on D1 and D8 tumor biopsies, identified genes associated with pCR using differential gene expression analysis, identified pathways associated with pCR using gene set enrichment and gene expression deconvolution methods, and compared the pCR predictive value of principal components derived from gene expression profiles by calculating and area under the curve for D1 and D8 subsets. Results: Twenty-three participants were enrolled, of whom 21 completed surgery following neoadjuvant therapy. Paired longitudinal fresh-frozen tumor samples (D1 and D8) were obtained from all patients. Among the 21 patients who underwent surgery, the pCR and the 4-year disease-free survival were 48% (90% CI 0.29-0.67) and 90% (95% CI 66-97%), respectively. The transcriptional profile of D8 biopsies was found to be more predictive of pCR (AUC = 0.91, 95% CI: 0.7993-1) than the D1 biopsies (AUC = 0.79, 95% CI: 0.5905-0.9822). Conclusions: In patients with HER2-positive IBC treated with neoadjuvant HP and paclitaxel for 16 weeks, gene expression patterns of tumor biopsies measured 1 week after treatment initiation not only offered different biological information but importantly served as a better predictor of pCR than baseline transcriptional analysis

Detailed SZ study of 19 LoCuSS galaxy clusters: masses and temperatures out to the virial radius

We present 16-GHz AMI SZ observations of 19 clusters with L_X >7x10^37 W (h50=1) selected from the LoCuS survey (0.142<z<0.295) and of A1758b, in the FoV of A1758a. We detect 17 clusters with 5-23sigma peak surface brightnesses. Cluster parameters are obtained using a Bayesian cluster analysis. We fit isothermal beta-models to our data and assume the clusters are virialized (with all the kinetic energy in gas internal energy). Our gas temperature, T_AMI, is derived from AMI SZ data, not from X-ray spectroscopy. Cluster parameters internal to r500 are derived assuming HSE. We find: (i) Different gNFW parameterizations yield significantly different parameter degeneracies. (ii) For h70 = 1, we find the virial radius r200 to be typically 1.6+/-0.1 Mpc and the total mass M_T(r200) typically to be 2.0-2.5xM_T(r500).(iii) Where we have found M_T X-ray (X) and weak-lensing (WL) values in the literature, there is good agreement between WL and AMI estimates (with M_{T,AMI}/M_{T,WL} =1.2^{+0.2}_{-0.3} and =1.0+/-0.1 for r500 and r200, respectively). In comparison, most Suzaku/Chandra estimates are higher than for AMI (with M_{T,X}/M_{T,AMI}=1.7+/-0.2 within r500), particularly for the stronger mergers.(iv) Comparison of T_AMI to T_X sheds light on high X-ray masses: even at large r, T_X can substantially exceed T_AMI in mergers. The use of these higher T_X values will give higher X-ray masses. We stress that large-r T_SZ and T_X data are scarce and must be increased. (v) Despite the paucity of data, there is an indication of a relation between merger activity and SZ ellipticity. (vi) At small radius (but away from any cooling flow) the SZ signal (and T_AMI) is less sensitive to ICM disturbance than the X-ray signal (and T_X) and, even at high r, mergers affect n^2-weighted X-ray data more than n-weighted SZ, implying significant shocking or clumping or both occur even in the outer parts of mergers.Comment: 45 pages, 33 figures, 13 tables Accepted for publication in MNRA

A Phase II Study of Sagopilone (ZK 219477; ZK-EPO) in Patients With Breast Cancer and Brain Metastases

Treatments for women with recurrent brain metastases from breast cancer are limited. In this phase II study, we administered sagopilone to patients with breast cancer and brain metastases. We observed modest activity with a central nervous system objective response rate of 13.3%; however, median PFS was disappointing. Further studies should focus on other agents to treat this challenging clinical problem

Complementary therapy use by patients and parents of children with asthma and the implications for NHS care: a qualitative study

BACKGROUND: Patients are increasingly using complementary therapies, often for chronic conditions. Asthma is the most common chronic condition in the UK. Previous research indicates that some asthma patients experience gaps in their NHS care. However, little attention has been given to how and why patients and parents of children with asthma use complementary therapies and the implications for NHS care. METHODS: Qualitative study, comprising 50 semi-structured interviews with a purposeful sample of 22 adults and 28 children with asthma (plus a parent), recruited from a range of NHS and non-NHS settings in Bristol, England. Data analysis was thematic, drawing on the principles of constant comparison. RESULTS: A range of complementary therapies were being used for asthma, most commonly Buteyko breathing and homeopathy. Most use took place outside of the NHS, comprising either self-treatment or consultation with private complementary therapists. Complementary therapies were usually used alongside not instead of conventional asthma treatment. A spectrum of complementary therapy users emerged, including "committed", "pragmatic" and "last resort" users. Motivating factors for complementary therapy use included concerns about conventional NHS care ("push factors") and attractive aspects of complementary therapies ("pull factors"). While participants were often uncertain whether therapies had directly helped their asthma, breathing techniques such as the Buteyko Method were most notably reported to enhance symptom control and enable reduction in medication. Across the range of therapies, the process of seeking and using complementary therapies seemed to help patients in two broad ways: it empowered them to take greater personal control over their condition rather than feel dependant on medication, and enabled exploration of a broader range of possible causes of their asthma than commonly discussed within NHS settings. CONCLUSION: Complementary therapy use reflects patients' and parents' underlying desire for greater self-care and need of opportunities to address some of their concerns regarding NHS asthma care. Self-management of chronic conditions is increasingly promoted within the NHS but with little attention to complementary therapy use as one strategy being used by patients and parents. With their desire for self-help, complementary therapy users are in many ways adopting the healthcare personas that current policies aim to encourage