Aristotle's view of human nature as a basis for ethical theory

The thesis examines Aristotle's ethical theory with primary reference to the Nicomachean Ethics (ED. It argues that the EX is intended not to improve its audience ethically, but rather to give it the political tools to pass an its already good life. The EN does this by articulating the goodness of that life and thus allowing the audience to enter effectively into ethical discussions. These form part of the process of passing on the good life by way of legislation in the polls and by more informal methods in institutions such as the household. The thesis examines in particular the accounts of practical reason, pleasure and the ergon argument in the Elf, and seeks to understand them in this context. It argues that by allowing the audience to improve the transmission of its values over the generations and by allowing its menbers to articulate the value of so doing, it moves the audience's life closer to divine perfection

Regulatory Divergence of Transcript Isoforms in a Mammalian Model System.

Phenotypic differences between species are driven by changes in gene expression and, by extension, by modifications in the regulation of the transcriptome. Investigation of mammalian transcriptome divergence has been restricted to analysis of bulk gene expression levels and gene-internal splicing. Using allele-specific expression analysis in inter-strain hybrids of Mus musculus, we determined the contribution of multiple cellular regulatory systems to transcriptome divergence, including: alternative promoter usage, transcription start site selection, cassette exon usage, alternative last exon usage, and alternative polyadenylation site choice. Between mouse strains, a fifth of genes have variations in isoform usage that contribute to transcriptomic changes, half of which alter encoded amino acid sequence. Virtually all divergence in isoform usage altered the post-transcriptional regulatory instructions in gene UTRs. Furthermore, most genes with isoform differences between strains contain changes originating from multiple regulatory systems. This result indicates widespread cross-talk and coordination exists among different regulatory systems. Overall, isoform usage diverges in parallel with and independently to gene expression evolution, and the cis and trans regulatory contribution to each differs significantly

Acupuncture for chronic pain and depression in primary care : a programme of research

Abstract Background There has been an increase in the utilisation of acupuncture in recent years, yet the evidence base is insufficiently well established to be certain about its clinical effectiveness and cost-effectiveness. Addressing the questions related to the evidence base will reduce uncertainty and help policy- and decision-makers with regard to whether or not wider access is appropriate and provides value for money. Aim Our aim was to establish the most reliable evidence on the clinical effectiveness and cost-effectiveness of acupuncture for chronic pain by drawing on relevant evidence, including recent high-quality trials, and to develop fresh evidence on acupuncture for depression. To extend the evidence base we synthesised the results of published trials using robust systematic review methodology and conducted a randomised controlled trial (RCT) of acupuncture for depression. Methods and results We synthesised the evidence from high-quality trials of acupuncture for chronic pain, consisting of musculoskeletal pain related to the neck and low back, osteoarthritis of the knee, and headache and migraine, involving nearly 18,000 patients. In an individual patient data (IPD) pairwise meta-analysis, acupuncture was significantly better than both sham acupuncture (p < 0.001) and usual care (p < 0.001) for all conditions. Using network meta-analyses, we compared acupuncture with other physical therapies for osteoarthritis of the knee. In both an analysis of all available evidence and an analysis of a subset of better-quality trials, using aggregate-level data, we found acupuncture to be one of the more effective therapies. We developed new Bayesian methods for analysing multiple individual patient-level data sets to evaluate heterogeneous continuous outcomes. An accompanying cost-effectiveness analysis found transcutaneous electrical nerve stimulation (TENS) to be cost-effective for osteoarthritis at a threshold of £20,000 per quality-adjusted life-year when all trials were synthesised. When the analysis was restricted to trials of higher quality with adequate allocation concealment, acupuncture was cost-effective. In a RCT of acupuncture or counselling compared with usual care for depression, in which half the patients were also experiencing comorbid pain, we found acupuncture and counselling to be clinically effective and acupuncture to be cost-effective. For patients in whom acupuncture is inappropriate or unavailable, counselling is cost-effective. Conclusion We have provided the most robust evidence from high-quality trials on acupuncture for chronic pain. The synthesis of high-quality IPD found that acupuncture was more effective than both usual care and sham acupuncture. Acupuncture is one of the more clinically effective physical therapies for osteoarthritis and is also cost-effective if only high-quality trials are analysed. When all trials are analysed, TENS is cost-effective. Promising clinical and economic evidence on acupuncture for depression needs to be extended to other contexts and settings. For the conditions we have investigated, the drawing together of evidence on acupuncture from this programme of research has substantially reduced levels of uncertainty. We have identified directions for further research. Our research also provides a valuable basis for considering the potential role of acupuncture as a referral option in health care and enabling providers and policy-makers to make decisions based on robust sources of evidence

Dissidents and God-Talk in the Johannine Epistles

Peer reviewe

Study protocol; thyroid hormone replacement for untreated older adults with subclinical hypothyroidism - a randomised placebo controlled trial (TRUST)

Background: Subclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH. Methods: Participants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4.6 and ≤19.9 mU/L) on a minimum of two measures ≥ three months apart, with fT4 levels within laboratory reference range. The study is a randomised double-blind placebo-controlled parallel group trial, starting with levothyroxine 50 micrograms daily (25 micrograms in subjects &lt;50Kg body weight or known coronary heart disease) with titration of dose in the active treatment group according to TSH level, and a mock titration in the placebo group. The primary outcomes are changes in two domains (hypothyroid symptoms and fatigue / vitality) on the thyroid-related quality of life questionnaire (ThyPRO) at one year. The study has 80% power (at p = 0.025, 2-tailed) to detect a change with levothyroxine treatment of 3.0% on the hypothyroid scale and 4.1% on the fatigue / vitality scale with a total target sample size of 750 patients. Secondary outcomes include general health-related quality of life (EuroQol), fatal and non-fatal cardiovascular events, handgrip strength, executive cognitive function (Letter Digit Coding Test), basic and instrumental activities of daily living, haemoglobin, blood pressure, weight, body mass index and waist circumference. Patients are monitored for specific adverse events of interest including incident atrial fibrillation, heart failure and bone fracture. Discussion: This large multicentre RCT of levothyroxine treatment of subclinical hypothyroidism is powered to detect clinically relevant change in symptoms / quality of life and is likely to be highly influential in guiding treatment of this common condition. Trial registration: Clinicaltrials.gov NCT01660126; registered 8th June 2012

Cardiovascular and Noncardiovascular Prescribing and Mortality After Takotsubo:Comparison With Myocardial Infarction and General Population

BACKGROUND: Takotsubo syndrome is an increasingly common cardiac emergency with no known evidence-based treatment.OBJECTIVES: To investigate cardiovascular mortality and medication use after takotsubo syndrome.METHODS: In a case-control study, all patients with takotsubo syndrome in Scotland between 2010-2017 (n=620) were age, sex and geographically matched to individuals in the general population (1:4, n=2,480) and contemporaneous patients with acute myocardial infarction (1:1, n=620). Electronic health record data linkage of mortality outcomes and drug prescribing were analysed using Cox proportional hazard regression models.RESULTS: Of the 3,720 study participants (mean age, 66 years; 91% women), 153 (25%) patients with takotsubo syndrome died over the median of 5.5 years follow up. This exceeded mortality rates in the general population [374 (15%)]; hazard ratio [HR] 1.78 [95% confidence interval 1.48-2.15], P&lt;0.0001), especially for cardiovascular (HR 2.47, [1.81-3.39], P&lt;0.001) but also non-cardiovascular (HR 1.48 [1.16-1.87], P=0.002) deaths. Mortality rates were lower for patients with takotsubo syndrome than those with myocardial infarction (31%, 195/620; HR 0.76 [0.62-0.94], P=0.012), which was attributable to lower rates of cardiovascular (HR 0.61 [0.44-0.84], P=0.002) but not non-cardiovascular (HR 0.92 [0.69-1.23], P=0.59) deaths. Despite comparable medications use, cardiovascular therapies were consistently associated with better survival in patients with myocardial infarction but not in those with takotsubo syndrome. Diuretic (P=0.01), anti-inflammatory (P=0.002) and psychotropic (P&lt;0.001) therapies were all associated with worse outcomes in patients with takotsubo syndrome.CONCLUSIONS: In patients with takotsubo syndrome, cardiovascular mortality is the leading cause of death, and this is not associated with cardiovascular therapy use

Variation in the SLC23A1 gene does not influence cardiometabolic outcomes to the extent expected given its association with L-ascorbic acid

Background: Observational studies showed that circulating l-ascorbic acid (vitamin C) is inversely associated with cardiometabolic traits. However, these studies were susceptible to confounding and reverse causation. Objectives:We assessed the relation between l-ascorbic acid and 10 cardiometabolic traits by using a single nucleotide polymorphism in the solute carrier family 23 member 1 (SLC23A1) gene (rs33972313) associated with circulating l-ascorbic acid concentrations. The observed association between rs33972313 and cardiometabolic outcomes was compared with that expected given the rs33972313-l-ascorbic acid and l-ascorbic acid–outcome associations. Design: A meta-analysis was performed in the following 5 independent studies: the British Women's Heart and Health Study (n = 1833), the MIDSPAN study (n = 1138), the Ten Towns study (n = 1324), the British Regional Heart Study (n = 2521), and the European Prospective Investigation into Cancer (n = 3737). Results: With the use of a meta-analysis of observational estimates, inverse associations were shown between l-ascorbic acid and systolic blood pressure, triglycerides, and the waist-hip ratio [the strongest of which was the waist-hip ratio (−0.13-SD change; 95% CI: −0.20-, −0.07-SD change; P = 0.0001) per SD increase in l-ascorbic acid], and a positive association was shown with high-density lipoprotein (HDL) cholesterol. The variation at rs33972313 was associated with a 0.18-SD (95% CI: 0.10-, 0.25-SD; P = 3.34 × 10−6) increase in l-ascorbic acid per effect allele. There was no evidence of a relation between the variation at rs33972313 and any cardiometabolic outcome. Although observed estimates were not statistically different from expected associations between rs33972313 and cardiometabolic outcomes, estimates for low-density lipoprotein cholesterol, HDL cholesterol, triglycerides, glucose, and body mass index were in the opposite direction to those expected. Conclusions: The nature of the genetic association exploited in this study led to limited statistical application, but despite this, when all cardiometabolic traits were assessed, there was no evidence of any trend supporting a protective role of l-ascorbic acid. In the context of existing work, these results add to the suggestion that observational relations between l-ascorbic acid and cardiometabolic health may be attributable to confounding and reverse causation

Oral health and elite sport performance

While the research base is limited, studies have consistently reported poor oral health in elite athletes since the first report from the 1968 Olympic Games. The finding is consistent both across selected samples attending dental clinics at major competitions and more representative sampling of teams and has led to calls from the International Olympic Committee for more accurate data on oral health. Poor oral health is an important issue directly as it can cause pain, negative effects on appearance and psychosocial effects on confidence and quality of life and may have long-term consequences for treatment burden. Self-reported evidence also suggests an impact on training and performance of athletes. There are many potential challenges to the oral health of athletes including nutritional, oral dehydration, exercise-induced immune suppression, lack of awareness, negative health behaviours and lack of prioritisation. However, in theory, oral diseases are preventable by simple interventions with good evidence of efficacy. The consensus statement aims to raise awareness of the issues of oral health in elite sport and recommends strategies for prevention and health promotion in addition to future research strategies

14th Annual Conference on Legal Issues For Financial Institutions

Materials from the 14th Annual Conference on Legal Issues For Financial Institutions held by UK/CLE in March 1994

In search of the authentic nation: landscape and national identity in Canada and Switzerland

While the study of nationalism and national identity has flourished in the last decade, little attention has been devoted to the conditions under which natural environments acquire significance in definitions of nationhood. This article examines the identity-forming role of landscape depictions in two polyethnic nation-states: Canada and Switzerland. Two types of geographical national identity are identified. The first – what we call the ‘nationalisation of nature’– portrays zarticular landscapes as expressions of national authenticity. The second pattern – what we refer to as the ‘naturalisation of the nation’– rests upon a notion of geographical determinism that depicts specific landscapes as forces capable of determining national identity. The authors offer two reasons why the second pattern came to prevail in the cases under consideration: (1) the affinity between wild landscape and the Romantic ideal of pure, rugged nature, and (2) a divergence between the nationalist ideal of ethnic homogeneity and the polyethnic composition of the two societies under consideration