De se attitudes and computation

There has been debate between those who maintain that indexical expressions are not essential and those who maintain that such indexicals cannot be dispensed with without an important loss of content. This version of the essentialist view holds that thoughts must also have indexical elements. Indexical thoughts appear to be in tension with the computational theory of mind (CTM). In this case we have the following inconsistent triad: (i) De se thoughts are essential. (ii) De se thoughts are indexical, they have a (Kaplanian) character. (iii) Computations can only take the syntactic type into account, they cannot take tokens into account. If (iii) is correct, then it seems we cannot make sense of a thought which uses a character such that its referent could vary from tokening to tokening. I argue that (iii) need not cause a problem, while maintaining the CTM. I claim that computations need not be sensitive to the features of a tokened symbol in the way that character demands. This job may be performed by a non‐modular part of the mind. Resolving the triad in this way provides a reason to accept that indexicals in thought are possible

Regulation of sex hormone binding globulin and insulin-like growth factor binding protein-1

Women with polycystic ovary syndrome (PCOS) present most commonly with hirsutism and/or anovulation. The prevalence of hirsutism and/or menstrual irregularity is increased in obese women with PCOS compared with lean women with PCOS. It is, therefore, possible that factors associated with obesity exacerbate the symptoms and the underlying hormonal abnormality of this condition. Sex hormone binding globulin (SHBG) and insulin-like growth factor binding protein-1 (IGFBP1) concentrations are reduced in PCOS and decline during puberty in boys and girls. The regulation of sex hormone binding globulin has been thought to be primarily by the sex steroid hormones and that of IGFBP1 by insulin. The hypothesis of this thesis is that dietary factors are more important than the sex steroids in the regulation of hepatic SHBG production and that this is of relevance in understanding the relationship between obesity and hirsutism in women with polcystic ovary syndrome. In addition insulin also regulates hepatic IGFBP1 production implying that the two binding proteins may be co-regulated. The role of sex steroids in the regulation of IGFBP1 is not known. The regulation of hepatic production of SHBG and IGFBP1 by insulin, IGF-1 and the sex steroids was studied in-vitro by cell culture experiments on Hepatocarcinoma G2 cells. The relationship of dietary factors on androgen metabolism and circulating SHBG and IGFBP1concentrations was investigated in three separate studies. In the first two studies women with PCOS were studied before and after calorie restriction and during an oral glucose tolerance test (OGTT). A third study conducted over a 24 hour period investigated the diurnal variation in SHBG and IGFBP1 related to that of insulin and IGF-1. The cell culture experiments demonstrated a role of insulin and IGF-1 as inhibitors of hepatic SHBG production but only insulin inhibited the secretion of IGFBP1. The effect of the sex steroids was less clear since testosterone increased SHBG production while oestradiol had no effect. The sex steroids had no effect on IGFBP1 production. Weight loss following a four week very low calorie diet was associated with a significant increase in SHBG and IGFBP1 concentrations mirrored by a decrease in insulin and IGF-1. This resulted in a decrease in free testosterone although the total testosterone concentration did not change. The inverse relationship of SHBG and IGFBP1 with insulin was further confirmed in the OGTT and 24 hour study although the role of IGF-1 was less clear. The time course of the changes was significantly longer for SHBG than IGFBP1. These studies demonstrate that insulin is a primary regulator of SHBG and IGFBP1 synthesis by the liver. The two binding proteins may be co-regulated by insulin but other factors including the sex steroids may alter their half-lives in the circulation and therefore their serum concentration under various physiological and pathological conditions

The Context-Sensitivity of Thought

I defend the claim that it is possible for thoughts to be context-sensitive. Assuming that a thought is a sentence of Mentalese (i.e. a well-formed string of mental representations) and content is a function from indices to truth-values, then a thought, T, is context-sensitive IFF at least one of the following three conditions are met: (i) T exhibits character-underdeterminacy, where T is character underdetermined iff a component of T makes an explicit reference to the context to establish content. (ii) T exhibits type-underdeterminacy, where T is type underdetermined iff there are tokens of T that have distinct truth-values. (iii) T is token-underdetermined, where T is token underdetermined iff for some possible states of affairs its truth-value is indeterminate. Additionally, there must be a mechanism by which the content of T can be determined by appeal to the context. Otherwise T is not sensitive to the context. The most significant objection to the possibility of context-sensitive thoughts comes from a regress argument. The concern is that any process of removing context-sensitivity from a thought will token an additional thought. If that further thought is context-sensitive, then another thought will have to be tokened. This process will only terminate when a non-context-sensitive thought is arrived at. Yet this seems to show that context-sensitivity in thought, if possible, can only be a contingent, detachable feature of thoughts. To counter this argument, I will present three versions of context-sensitive thought, mirroring each of (i)-(iii). These views make use of a range of relationships between thoughts and their contents or extensions that are affected by the context, but I will argue they do not require the generation of an additional thought. This provides a range of views on which thoughts can be treated as essentially context-sensitive

Cost-effectiveness of a new autoantibody test added to Computed Tomography (CT) compared to CT surveillance alone in the diagnosis of lung cancer amongst patients with indeterminate pulmonary nodules

Oncimmune's EarlyCDT®-Lung is a simple ELISA blood test that measures seven lung cancer specific autoantibodies and is used in the assessment of malignancy risk in patients with indeterminate pulmonary nodules (IPNs). The objective of this study was to examine the cost-effectiveness of EarlyCDT-Lung in the diagnosis of lung cancer amongst patients with IPNs in addition to CT surveillance, compared to CT surveillance alone which is the current recommendation by the British Thoracic Society guidelines. A model consisting of a combination of a decision tree and Markov model was developed using the outcome measure of the quality adjusted life year (QALY). A life-time time horizon was adopted. The model was parameterized using a range of secondary sources. At £70 per test, EarlyCDT-Lung and CT surveillance was found to be cost-effective compared to CT surveillance alone with an incremental cost-effectiveness ratio (ICER) of less than £2,500 depending on the test accuracy parameters used. It was also found that EarlyCDT-Lung can be priced up to £1,177 and still be cost-effective based on cost-effectiveness acceptance threshold of £20,000 / QALY. Further research to resolve parameter uncertainty, was not found to be of value. The results here demonstrate that at £70 per test the EarlyCDT-Lung will have a positive impact on patient outcomes and coupled with CT surveillance is a cost-effective approach to the management of patients with IPNs. The conclusions drawn from this analysis are robust to realistic variation in the parameters used in the model

The efficient use of the maternity workforce and the implications for safety and quality in maternity care : a population-based, cross-sectional study

Background: The performance of maternity services is seen as a touchstone of whether or not we are delivering high-quality NHS care. Staffing has been identified in numerous reports as being a critical component of safe, effective, user-centred care. There is little evidence regarding the impact of maternity workforce staffing and skill mix on the safety, quality and cost of maternity care in the UK. Objectives: To understand the relationship between organisational factors, maternity workforce staffing and skill mix, cost and indicators of safe and high-quality care. Design and methods: Data included Hospital Episode Statistics (HES) from 143 NHS trusts in England in 2010–11 (656,969 delivery records), NHS Workforce Statistics, England, 2010–11, Care Quality Commission Maternity Survey of women’s experiences 2010 and NHS reference costs 2010/11. Ten indicators were derived from HES data. They included healthy mother and healthy baby outcomes and mode of birth. Adjustments were made for background characteristics and clinical risk. Data were analysed to examine the influence of organisational factors, staffing and costs using multilevel logistic regression models. A production function analysis examined the relationship between staffing, skill mix and output. Results: Outcomes were largely determined by women’s level of clinical risk [based on National Institute for Health and Care Excellence (NICE) guidance], parity and age. The effects of trust size and trust university status were small. Larger trust size reduced the chance of a healthy mother outcome and also reduced the likelihood of a healthy mother/healthy baby dyad outcome, and increased the chances of other childbirth interventions. Increased investment in staff did not necessarily have an effect on the outcome and experience measures chosen, although there was a higher rate of intact perineum and also of delivery with bodily integrity in trusts with greater levels of midwifery staffing. An analysis of the multiplicative effects of parity and clinical risk with the staffing variables was more revealing. Increasing the number of doctors had the greatest impact on outcomes in higher-risk women and increasing the number of midwives had the greatest impact on outcomes in lower-risk women. Although increased numbers of support workers impacted on reducing childbirth interventions in lower-risk women, they also had a negative impact on the healthy mother/healthy baby dyad outcomes in all women. In terms of maximising the capacity of a trust to deliver babies, midwives and support workers were found to be substitutes for each other, as were consultants and other doctors. However, any substitution between staff groups could impact on the quality of care given. Economically speaking, midwives are best used in combination with consultants and other doctors. Conclusions: Staffing levels have positive and negative effects on some outcomes, and deployment of doctors and midwives where they have most beneficial impact is important. Managers may wish to exercise caution in increasing the number of support workers who care for higher-risk women. There also appear to be limited opportunities for role substitution. Future work: Wide variations in outcomes remain after adjustment for sociodemographic and clinical risk, and organisational factors. Further research is required on what may be influencing unexplained variation such as organisational climate and culture, use of NICE guidelines in practice, variation of models of care within trusts and women’s choices. Funding: The National Institute for Health Research Health Services and Delivery Research programme

The impact of female obesity on the outcome of fertility treatment

Peer reviewedPublisher PD

Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan

Polycystic ovary syndrome (PCOS) is of clinical and public health importance as it is very common, affecting up to one in five women of reproductive age. It has significant and diverse clinical implications including reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, adverse cardiovascular risk profiles) and psychological features (increased anxiety, depression and worsened quality of life). Polycystic ovary syndrome is a heterogeneous condition and, as such, clinical and research agendas are broad and involve many disciplines. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental factors including lifestyle and bodyweight. Importantly, PCOS has unique interactions with the ever increasing obesity prevalence worldwide as obesity-induced insulin resistance significantly exacerbates all the features of PCOS. Furthermore, it has clinical implications across the lifespan and is relevant to related family members with an increased risk for metabolic conditions reported in first-degree relatives. Therapy should focus on both the short and long-term reproductive, metabolic and psychological features. Given the aetiological role of insulin resistance and the impact of obesity on both hyperinsulinaemia and hyperandrogenism, multidisciplinary lifestyle improvement aimed at normalising insulin resistance, improving androgen status and aiding weight management is recognised as a crucial initial treatment strategy. Modest weight loss of 5% to 10% of initial body weight has been demonstrated to improve many of the features of PCOS. Management should focus on support, education, addressing psychological factors and strongly emphasising healthy lifestyle with targeted medical therapy as required. Monitoring and management of long-term metabolic complications is also an important part of routine clinical care. Comprehensive evidence-based guidelines are needed to aid early diagnosis, appropriate investigation, regular screening and treatment of this common condition. Whilst reproductive features of PCOS are well recognised and are covered here, this review focuses primarily on the less appreciated cardiometabolic and psychological features of PCOS