Under the influence? The construction of foetal alcohol syndrome in UK newspapers

Today, alongside many other proscriptions, women are expected to abstain or at least limit their alcohol consumption during pregnancy. This advice is reinforced through warning labels on bottles and cans of alcoholic drinks. In most (but not all) official policies, this is linked to a risk of Foetal Alcohol Syndrome (FAS) or one of its associated conditions. However, given that there is little medical evidence that low levels of alcohol consumption have an adverse impact on the foetus, we need to examine broader societal ideas to explain why this has now become a policy concern. This paper presents a quantitative and qualitative assessment of analysis of the media in this context. By analysing the frames over time, this paper will trace the emergence of concerns about alcohol consumption during pregnancy. It will argue that contemporary concerns about FAS are framed around a number of pre-existing discourses including alcohol consumption as a social problem, heightened concerns about children at risk and shifts in ideas about the responsibility of motherhood including during the pre-conception and pregnancy periods. Whilst the newspapers regularly carried critiques of the abstinence position now advocated, these challenges focused did little to refute current parenting cultures.

Advocating alcohol abstinence to pregnant women: some observations about British policy

In 2007, the English Department of Health (DH) issued advice stating 'pregnant woman' and 'those trying to conceive' should abstain from drinking alcohol. As others have noted, this advice was issued despite their being no new evidence about the deleterious effects of low levels of alcohol consumption. In this paper, we argue this development is significant for the social construction of 'risk', since in advocating abstinence without an evidence base for this advice, policy makers formalise a connection between uncertainty and danger. We suggest this development has important implications, most obviously for pregnant women, certainly impacting on the nature of the advice they will now receive and likely more generally on their experience of the transition to motherhood. We suggest it has wider implications for individuals' experience also, as policy makers appear to be advocating the same approach to risk to non-pregnant people. Further, it suggests a noteworthy formalisation of a new definition of risk, which should be debated far more extensively, as it matters for the future development of health policy.

The significance of microaneurysms and haemorrhages within one optic disc diameter of the fovea

Free paper session INTRODUCTION. Microaneurysms and haemorrhages within the macula area are a poor predictor of macular oedema as shown by optical coherence tomography (OCT). Our research suggests that it is safe and cost effective to screen patients who present with these surrogate markers annually. PURPOSE. To determine whether microaneurysms (ma) and haemorrhages (hm) within one optic disc diameter of the fovea (ma/hm<1DD) are significant predictors of macular oedema. METHODS. Data were collected over a one-year period from patients attending digital diabetic retinopathy screening. Patients who presented with ma/hm<1DD also had an OCT scan. The fast macula scan on the Stratus OCT was used and an ophthalmologist reviewed the scans to determine whether macular oedema was present. Macular oedema was identified by thickening on the OCT cross-sections. Patients were split into two groups. Group one (325 eyes) included those with best VA?6/9 and group two (30 eyes) with best VA =6/12. Only patients who had no other referable features of diabetic retinopathy were selected. RESULTS. In group one, 6 (1.8%) out of 325 eyes showed thickening on the OCT and were referred to hospital eye service (HES) for further investigation. In group two, 6 (20%) out of 30 eyes showed thickening and were referred to HES. CONCLUSIONS. Ma/hm<1DD become more significant predictors of macular oedema when VA is reduced. Results confirm the grading criteria concerning microaneurysms predicting macular oedema for referable maculopathy in the English national screening programme. OCT is a useful method to accurately identify patients requiring referral to HES.

Changes in gene expression and morphology of mouse embryonic stem cells on differentiation into insulin-producing cells in vitro and in vivo

Background Embryonic stem (ES) cells have the potential to produce unlimited numbers of surrogate insulin-producing cells for cell replacement therapy of type I diabetes mellitus. The impact of the in vivo environment on mouse ES cell differentiation towards insulin-producing cells was analysed morphologically after implantation. Methods ES cells differentiated in vitro into insulin-producing cells according to the Lumelsky protocol or a new four-stage differentiation protocol were analysed morphologically before and after implantation for gene expression by in situ reverse transcription polymerase chain reaction and protein expression by immunohistochemistry and ultrastructural analysis. Results In comparison with nestin positive ES cells developed according to the reference protocol, the number of ES cells differentiated with the four-stage protocol increased under in vivo conditions upon morphological analysis. The cells exhibited, in comparison to the in vitro situation, increased gene and protein expression of Pdx1, insulin, islet amyloid polypeptide (IAPP), the GLUT2 glucose transporter and glucokinase, which are functional markers for glucose-induced insulin secretion of pancreatic beta cells. Renal sub-capsular implantation of ES cells with a higher degree of differentiation achieved by in vitro differentiation with a four-stage protocol enabled further significant maturation for the beta-cell-specific markers, insulin and the co-stored IAPP as well as the glucose recognition structures. in contrast, further in vivo differentiation was not achieved with cells differentiated in vitro by the reference protocol. Conclusions A sufficient degree of in vitro differentiation is an essential prerequisite for further substantial maturation in a beta-cell-specific way in vivo, supported by cell-cell contacts and vascularisation. Copyright (c) 2009 John Wiley & Sons, Ltd.

Women's experiential journey toward voluntary childlessness

Voluntary childlessness is a relatively novel yet growing phenomenon. This idiographic study explored three women's experiential journeys toward voluntary childlessness. Semi-structured interviews were carried out and analysed using Interpretative Phenomenological Analysis. Themes identified were: Owning the choice to be childless, social expectations, and models of mothering. Despite defining ‘voluntary childlessness’ as an unequivocal decision, the women's experiential accounts revealed an intrinsic fluidity in their journeys toward childlessness. Factors including beliefs in equality, independence and career aspirations competed with constructs of mothering/motherhood, partnership and choice to create a complex tapestry of contributory factors in these women's childlessness. The findings question the notion of choice and particularly women's ownership of that choice. The journeys toward childlessness these women shared reveal a synthesis of agentic decision-making, personal histories and challenging lifestyle choices bound up within an existential need to be a woman. More research is needed to determine the place of voluntary childlessness within society. Copyright © 2010 John Wiley & Sons, Ltd

Value of glycaemic control in diabetes

Full text: Several Lancet publications have questioned the value of glycaemic control in diabetic patients. For example, in their Comment (Sept 29, p 1103),1 John Cleland and Stephen Atkin state that “Improved glycaemic control is not a surrogate for effective care of patients who have diabetes”, and Victor Montori and colleagues (p 1104)2 claim that “HbA1c loses its validity as a surrogate marker when patients have a constellation of metabolic abnormalities”. We are concerned that the reaction against “glucocentricity” in the field of diabetes has gone too far. Even the UK's National Prescribing Centre website, carrying the National Health Service logo, includes comments that undermine the value of glycaemic control. For example, referring to the United Kingdom Prospective Diabetes Study (UKPDS), this site states that “Compared with ‘conventional control’ there was no benefit from tight control of blood glucose with sulphonylureas or insulin with regard to total mortality, diabetes-related death, macrovascular outcomes or microvascular outcomes, including all the most serious ones such as blindness or kidney failure”.3 It is well established that better glycaemic control reduces long-term microvascular complications in type 1 and type 2 diabetes.4 In type 2 diabetes, the UKPDS reported that a composite microvascular endpoint (retinopathy requiring photocoagulation, vitreous haemorrhage, and fatal or non-fatal renal failure) was reduced by 25% in patients randomised to intensive glucose control (p=0·0099).4 To imply that these are not patient-relevant outcomes is to distort the evidence. Many studies have also found that improved glycaemic control reduces macrovascular complications.5 Do not be misled: glycaemic control remains a crucial component in the care of people with diabetes. The authors have received research support and undertaken ad hoc consultancies and speaker engagements for several pharmaceutical companies.

The effect of spectral filters on reading speed and accuracy following stroke

Purpose - The aim of the study was to determine the effect of optimal spectral filters on reading performance following stroke. Methods - Seventeen stroke subjects, aged 43-85, were considered with an age-matched Control Group (n = 17). Subjects undertook the Wilkins Rate of Reading Test on three occasions: (i) using an optimally selected spectral filter; (ii) subjects were randomly assigned to two groups: Group 1 used an optimal filter, whereas Group 2 used a grey filter, for two-weeks. The grey filter had similar photopic reflectance to the optimal filters, intended as a surrogate for a placebo; (iii) the groups were crossed over with Group 1 using a grey filter and Group 2 given an optimal filter, for two weeks, before undertaking the task once more. An increase in reading speed of >5% was considered clinically relevant. Results - Initial use of a spectral filter in the stroke cohort, increased reading speed by ~8%, almost halving error scores, findings not replicated in controls. Prolonged use of an optimal spectral filter increased reading speed by >9% for stroke subjects; errors more than halved. When the same subjects switched to using a grey filter, reading speed reduced by ~4%. A second group of stroke subjects used a grey filter first; reading speed decreased by ~3% but increased by ~4% with an optimal filter, with error scores almost halving. Conclusions - The present study has shown that spectral filters can immediately improve reading speed and accuracy following stroke, whereas prolonged use does not increase these benefits significantly. © 2013 Spanish General Council of Optometry.

Uncertainty analysis in the Model Web

This thesis provides a set of tools for managing uncertainty in Web-based models and workflows.To support the use of these tools, this thesis firstly provides a framework for exposing models through Web services. An introduction to uncertainty management, Web service interfaces,and workflow standards and technologies is given, with a particular focus on the geospatial domain.An existing specification for exposing geospatial models and processes, theWeb Processing Service (WPS), is critically reviewed. A processing service framework is presented as a solutionto usability issues with the WPS standard. The framework implements support for Simple ObjectAccess Protocol (SOAP), Web Service Description Language (WSDL) and JavaScript Object Notation (JSON), allowing models to be consumed by a variety of tools and software. Strategies for communicating with models from Web service interfaces are discussed, demonstrating the difficultly of exposing existing models on the Web. This thesis then reviews existing mechanisms for uncertainty management, with an emphasis on emulator methods for building efficient statistical surrogate models. A tool is developed to solve accessibility issues with such methods, by providing a Web-based user interface and backend to ease the process of building and integrating emulators. These tools, plus the processing service framework, are applied to a real case study as part of the UncertWeb project. The usability of the framework is proved with the implementation of aWeb-based workflow for predicting future crop yields in the UK, also demonstrating the abilities of the tools for emulator building and integration. Future directions for the development of the tools are discussed.

Moderate relationships between NAA and cognitive ability in healthy adults:implications for cognitive spectroscopy

Background: Proton Magnetic Resonance Spectroscopy (H-MRS) is a non-invasive imaging technique that enables quantification of neurochemistry in vivo and thereby facilitates investigation of the biochemical underpinnings of human cognitive variability. Studies in the field of cognitive spectroscopy have commonly focused on relationships between measures of N-acetyl aspartate (NAA), a surrogate marker of neuronal health and function, and broad measures of cognitive performance, such as IQ. Methodology/Principal Findings: In this study, we used H-MRS to interrogate single-voxels in occipitoparietal and frontal cortex, in parallel with assessments of psychometric intelligence, in a sample of 40 healthy adult participants. We found correlations between NAA and IQ that were within the range reported in previous studies. However, the magnitude of these effects was significantly modulated by the stringency of data screening and the extent to which outlying values contributed to statistical analyses. Conclusions/Significance: H-MRS offers a sensitive tool for assessing neurochemistry non-invasively, yet the relationships between brain metabolites and broad aspects of human behavior such as IQ are subtle. We highlight the need to develop an increasingly rigorous analytical and interpretive framework for collecting and reporting data obtained from cognitive spectroscopy studies of this kind. © 2014 Patel, Blyth, Griffiths, Kelly and Talcott.

Mechanism of induction of muscle protein degradation by angiotensin II

Angiotensin I and II have been shown to directly induce protein degradation in skeletal muscle through an increased activity and expression of the ubiquitin-proteasome proteolytic pathway. This investigation determines the role of the nuclear transcription factor nuclear factor-κB (NF-κB) in this process. Using murine myotubes as a surrogate model system both angiotensin I and II were found to induce activation of protein kinase C (PKC), with a parabolic dose-response curve similar to the induction of total protein degradation. Activation of PKC was required for the induction of proteasome expression, since calphostin C, a highly specific inhibitor of PKC, attenuated both the increase in total protein degradation and in proteasome expression and functional activity increased by angiotensin II. PKC is known to activate I-κB kinase (IKK), which is responsible for the phosphorylation and subsequent degradation of I-κB. Both angiotensin I and II induced an early decrease in cytoplasmic I-κB levels followed by nuclear accumulation of NF-κB. Using an NF-κB luciferase construct this was shown to increase transcriptional activation of NF-κB regulated genes. Maximal luciferase expression was seen at the same concentrations of angiotensin I/II as those inducing protein degradation. Total protein degradation induced by both angiotensin I and II was attenuated by resveratrol, which prevented nuclear accumulation of NF-κB, confirming that activation of NF-κB was responsible for the increased protein degradation. These results suggest that induction of proteasome expression by angiotensin I/II involves a signalling pathway involving PKC and NF-κB. © 2005 Elsevier Inc. All rights reserved.

Angiotensin II directly inhibits protein synthesis in murine myotubes

Angiotensin II (Ang II) has been implicated in muscle protein loss in cachexia. To determine whether the Ang I/II system directly inhibits protein synthesis in muscle their effect has been monitored in vitro using murine myotubes as a surrogate model system. Ang I inhibited protein synthesis by 40-50% over the concentration range of 0.05-2.5 μM within 30 min of addition, and the inhibition remained relatively constant over 24 h. The effect was attenuated by co-incubation with the angiotensin converting enzyme inhibitor imidaprilat (50 μM) suggesting that inhibition of protein synthesis was due to the formation of Ang II. Ang II also inhibited protein synthesis by 40-50% over the concentration range of 0.1-5 μM, and the inhibition also remained relatively constant between 30 min and 24 h after addition. The effect was attenuated by insulin-like growth factor-1 (IGF-1) (25-100 ng/ml). Thus, Ang I/II have the ability to induce muscle atrophy through inhibition of protein synthesis. © 2005 Elsevier Ireland Ltd. All rights reserved.

Metformin:effects on micro and macrovascular complications in type 2 diabetes

Introduction: The antihyperglycaemic agent metformin is widely used in the treatment of type 2 diabetes. Data from the UK Prospective Diabetes Study and retrospective analyses of large healthcare databases concur that metformin reduces the incidence of myocardial infarction and increases survival in these patients. This apparently vasoprotective effect appears to be independent of the blood glucose-lowering efficacy. Effects of metformin: Metformin has long been known to reduce the development of atherosclerotic lesions in animal models, and clinical studies have shown the drug to reduce surrogate measures such as carotid intima-media thickness. The anti-atherogenic effects of metformin include reductions in insulin resistance, hyperinsulinaemia and obesity. There may be modest favourable effects against dyslipidaemia, reductions in pro-inflammatory cytokines and monocyte adhesion molecules, and improved glycation status, benefiting endothelial function in the macro- and micro-vasculature. Additionally metformin exerts anti-thrombotic effects, contributing to overall reductions in athero-thrombotic risk in type 2 diabetic patients. © 2008 Springer Science+Business Media, LLC.

Correlates of depression in bipolar disorder

We analyse time series from 100 patients with bipolar disorder for correlates of depression symptoms. As the sampling interval is non-uniform, we quantify the extent of missing and irregular data using new measures of compliance and continuity. We find that uniformity of response is negatively correlated with the standard deviation of sleep ratings (ρ = -0.26, p = 0.01). To investigate the correlation structure of the time series themselves, we apply the Edelson-Krolik method for correlation estimation. We examine the correlation between depression symptoms for a subset of patients and find that self-reported measures of sleep and appetite/weight show a lower average correlation than other symptoms. Using surrogate time series as a reference dataset, we find no evidence that depression is correlated between patients, though we note a possible loss of information from sparse sampling. © 2013 The Author(s).

Structural design of contact lens-based drug delivery systems; in vitro and in vivo studies of ocular triggering mechanisms

This study identifies and investigates the potential use of in-eye trigger mechanisms to supplement the widely available information on release of ophthalmic drugs from contact lenses under passive release conditions. Ophthalmic dyes and surrogates have been successfully employed to investigate how these factors can be drawn together to make a successful system. The storage of a drug-containing lens in a pH lower than that of the ocular environment can be used to establish an equilibrium that favours retention of the drug in the lens prior to ocular insertion. Although release under passive conditions does not result in complete dye elution, the use of mechanical agitation techniques which mimic the eyelid blink action in conjunction with ocular tear chemistry promotes further release. In this way differentiation between passive and triggered in vitro release characteristics can be established. Investigation of the role of individual tear proteins revealed significant differences in their ability to alter the equilibrium between matrix-held and eluate-held dye or drug. These individual experiments were then investigated in vivo using ophthalmic dyes. Complete elution was found to be achievable in-eye; this demonstrated the importance of that fraction of the drug retained under passive conditions and the triggering effect of in-eye conditions on the release process. Understanding both the structure-property relationship between drug and material and in-eye trigger mechanisms, using ophthalmic dyes as a surrogate, provides the basis of knowledge necessary to design ocular drug delivery vehicles for in-eye release in a controllable manner.

Improving the economic value of photographic screening for optical coherence tomography-detectable macular oedema:a prospective, multicentre, UK study

Objectives: To determine the best photographic surrogate markers for detecting sight-threatening macular oedema (MO) in people with diabetes attending UK national screening programmes. Design: A multicentre, prospective, observational cohort study of 3170 patients with photographic signs of diabetic retinopathy visible within the macular region [exudates within two disc diameters, microaneurysms/dot haemorrhages (M/DHs) and blot haemorrhages (BHs)] who were recruited from seven study centres. Setting: All patients were recruited and imaged at one of seven study centres in Aberdeen, Birmingham, Dundee, Dunfermline, Edinburgh, Liverpool and Oxford. Participants: Subjects with features of diabetic retinopathy visible within the macular region attending one of seven diabetic retinal screening programmes. Interventions: Alternative referral criteria for suspected MO based on photographic surrogate markers; an optical coherence tomographic examination in addition to the standard digital retinal photograph. Main outcome measures: (1) To determine the best method to detect sight-threatening MO in people with diabetes using photographic surrogate markers. (2) Sensitivity and specificity estimates to assess the costs and consequences of using alternative strategies. (3) Modelled long-term costs and quality-adjusted life-years (QALYs). Results: Prevalence of MO was strongly related to the presence of lesions and was roughly five times higher in subjects with exudates or BHs or more than two M/DHs within one disc diameter. Having worse visual acuity was associated with about a fivefold higher prevalence of MO. Current manual screening grading schemes that ignore visual acuity or the presence of M/DHs could be improved by taking these into account. Health service costs increase substantially with more sensitive/less specific strategies. A fully automated strategy, using the automated detection of patterns of photographic surrogate markers, is superior to all current manual grading schemes for detecting MO in people with diabetes. The addition of optical coherence tomography (OCT) to each strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. Conclusions: Compared with all current manual grading schemes, for the same sensitivity, a fully automated strategy, using the automated detection of patterns of photographic surrogate markers, achieves a higher specificity for detecting MO in people with diabetes, especially if visual acuity is included in the automated strategy. Overall, costs to the health service are likely to increase if more sensitive referral strategies are adopted over more specific screening strategies for MO, for only very small gains in QALYs. The addition of OCT to each screening strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. © Queen's Printer and Controller of HMSO 2013.