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Members of online bipolar disorder forums often report experiences of mood-stabilisation on the ketogenic diet, which has traditionally been used in the treatment of epilepsy. We examined the nature and extent of such reports.
To investigate associations between a ketogenic diet and mood stabilisation among individuals with bipolar disorder.
We undertook an observational analytic study of free-text comments in online forums about mood effects of dietary interventions (ketogenic, omega-3 enriched or vegetarian) classified by a priori categories of change in mood stabilisation in 274 people with bipolar disorder.
There were 141 (85.5%) free-text comments on ketogenic diets that reported a positive impact on mood stabilisation. Reports of significant mood stabilisation or remission of symptoms over a period were substantially higher for a ketogenic diet than for other diets (93/165, 56.4%, 95% CI 48.4–64.1) v. 14/94, 14.9%, 95% CI 8.4–23.7), odds ratio 7.4, 95% CI 3.8–14.1, P < 0.0001), many with detailed reports of the improvements experienced and several lasting for extended periods (months to years). Other reported associations included fewer episodes of depression (in 41.2%, 95% CI 30.6–52.4 of individuals); improved clarity of thought and speech (28.2%, 95% CI 19.0–39.0); increased energy (25.9, 95% CI 17.0–36.5); and weight loss (25.9%, 95% CI 17.0–36.5).
Despite the inherent limitations of the observational data based on self-reports posted online, the association strength and reports of sustained benefit support a hypothesis of a ketogenic diet being associated with beneficial effects on mood stabilisation. Caution should be exercised in interpreting this data until a controlled trial can be carried out to examine this hypothesis. These preliminary observations are generally consistent with a mitochondrial dysfunction component to bipolar disorder aetiology with ketones bypassing a block between glycolysis and the tricarboxylic acid cycle.
Impetigo is common in remote Indigenous children of northern Australia, with the primary driver in this context being Streptococcus pyogenes [or group A Streptococcus (GAS)]. To reduce the high burden of impetigo, the transmission dynamics of GAS must be more clearly elucidated. We performed whole genome sequencing on 31 GAS isolates collected in a single community from children in 11 households with ⩾2 GAS-infected children. We aimed to determine whether transmission was occurring principally within households or across the community. The 31 isolates were represented by nine multilocus sequence types and isolates within each sequence type differed from one another by only 0–3 single nucleotide polymorphisms. There was evidence of extensive transmission both within households and across the community. Our findings suggest that strategies to reduce the burden of impetigo in this setting will need to extend beyond individual households, and incorporate multi-faceted, community-wide approaches.
Nickel based alloys with nominal compositions similar to 78Ni -15Cr -7Fe, commonly referred to as “Inconel”, exhibit serrated flow (Portevin-LeChatelier effect) in the temperature interval of 230-730°C. Within this temperature range a series of thermally activated processes can also be observed when a wire sample of the alloy is heated with the direct resistance method under dead-weight loading while stressed above the room temperature yield. These processes include the expected initial period of plastic deformation at the start of heating followed by its complete arrest at a higher temperature, a behavior that is completely at odds with models for the thermal activation of plastic flow in metals. As the temperature is increased after this first arrest a cascade of two or three large plastic instabilities involving the high velocity propagation of narrow deformation bands is observed. Measurements of the band velocities using the time of flight within a 50.8 mm gage length extensometer indicate that they can exceed 2 m/s in some cases. Estimates of the maximum local strain rate attained within the deformation bands, obtained with a diametral extensometer, approach 15-18 s−1. The localization of plastic flow into narrow, high velocity bands in this material is the result of the collective behavior of dislocations interacting at a high density. As demonstrated by TEM examination of the complex dislocation structures associated with these various events, however, it is difficult to rationalize a specific mechanism for these effects. If one assumes that both serrated flow and the thermally activated strain bursts are manifestations of the same basic mechanism these observations pose a challenging problem for interpretation with models for the Portevin-LeChatelier effect in this material.
The UK was one of few European countries to document a substantial wave of pandemic (H1N1) 2009 influenza in summer 2009. The First Few Hundred (FF100) project ran from April–June 2009 gathering information on early laboratory-confirmed cases across the UK. In total, 392 confirmed cases were followed up. Children were predominantly affected (median age 15 years, IQR 10–27). Symptoms were mild and similar to seasonal influenza, with the exception of diarrhoea, which was reported by 27%. Eleven per cent of all cases had an underlying medical condition, similar to the general population. The majority (92%) were treated with antiviral drugs with 12% reporting adverse effects, mainly nausea and other gastrointestinal complaints. Duration of illness was significantly shorter when antivirals were given within 48 h of onset (median 5 vs. 9 days, P=0·01). No patients died, although 14 were hospitalized, of whom three required mechanical ventilation. The FF100 identified key clinical and epidemiological characteristics of infection with this novel virus in near real-time.
The current rate of advances in genetic technology and statistical methods makes it difficult to discuss study design in mapping complex disease traits in a way that will have value beyond a relatively short time horizon. This chapter considers how knowledge about the nature of complex diseases and traits can inform study design and confines itself to genomic (rather than proteomic or metabonomic) approaches.
Genetic influences on complex traits can be considered in terms of susceptibility to disease (clinical and pre-clinical), susceptibility to differences in natural history of disease (severity, complications and prognosis), susceptibility to different therapeutic responses (efficacy and adverse effects) or in terms of the genetic determinants of normal phenotypic variation in health.
The choices between approaches depend not only on the context of the study, but also on the relative costs of ascertaining families, measuring phenotypes and genotyping. The costs of genotyping have been falling rapidly over the last decade and the trend is for genotyping to be done in a few automated high-throughput centres to maximize efficiency. In contrast, more stringent ethical and data protection legislation requirements have tended to increase unit recruitment costs, since ascertainment and recruitment procedures become more demanding and remain very labor intensive. It is likely therefore that the requirements for very large sample sizes and for large collaborative studies will increasingly involve research groups from countries of intermediate development which can assure high fidelity phenotyping, but at much lower cost than is possible in most industrialized nations.
Activity patterns of domesticated animals have largely focussed on hours of daylight and relatively few studies include detailed observations of night time activity. This has the potential to overlook behaviours of significance to the assessment of welfare. For example, stereotypic activities in laboratory mice are largely confined to dark periods, and consequently are not commonly reported by daytime laboratory workers. Use of low light video cameras coupled with infra-red or low intensity lighting now makes observation over entire light-dark cycle practical, whilst minimising disturbance to the sampled population. This paper describes the activity patterns of stabled horses over 24 hour periods. These observations can then be used as baseline for investigating the effects of changes to the stable environment on horses’ behaviour and welfare.
The contribution of air conduction auditory brainstem response (AC-ABR) testing in the paediatric population is widely accepted in clinical audiology. However, this does not allow for differentiation between conductive and sensorineural hearing loss. The purpose ofthis paper is to review the role of bone conduction auditory brainstem responses (BC-ABR). It is argued that despite such technical difficulties as a narrow dynamic range, masking dilemmas, stimulus artifact and low frequency underestimation of hearing loss, considerable evidence exists to suggest that BC-ABR testing provides an important contribution in the accurate assessmentof hearing loss in infants. Modification of the BC-ABR protocol is discussed and the technical difficulties that may arise are addressed, permitting BC-ABR to be used as a tool in the differential diagnosis between conductive and sensorineural hearing. Two relevant case studies are presented to highlight the growing importance of appropriate management in early identification of hearing loss. It can be concluded that BC-ABR should be adopted as a routine clinical diagnostic tool.
Social benefit-cost analysis is a process of identifying, measuring and comparing the social benefits and costs of an investment project or program. A program is a series of projects undertaken over a period of time with a particular objective in view. The project or projects in question may be public projects – undertaken by the public sector – or private projects. Both types of projects need to be appraised to determine whether they represent an efficient use of resources. Projects that represent an efficient use of resources from a private viewpoint may involve costs and benefits to a wider range of individuals than their private owners. For example, a private project may pay taxes, provide employment for the otherwise unemployed, and generate pollution. These effects are termed social benefits and costs to distinguish them from the purely private costs and returns of the project. Social benefit-cost analysis is used to appraise private projects from a social viewpoint as well as to appraise public projects.
It should be noted that the technique of social benefit-cost analysis can also be used to analyse the effects of changes in public policies such as the tax/subsidy or regulatory regimes. However a very broad range of issues can arise in this kind of analysis and, for ease of exposition, we adopt the narrower perspective of project analysis in this study.
Public projects are often thought of in terms of the provision of physical capital in the form of infrastructure such as bridges, highways and dams. However there are other less obvious types of physical projects that augment environmental capital stocks and involve activities such as land reclamation, pollution control, fishery management and provision of the parks.
In this Chapter we consider three issues each of which may call for a modification of the following simple net present value rule: in the absence of risk, undertaking any project with a positive net present value (NPV), calculated using the appropriate shadow-prices and discounting at the market rate of interest, will contribute to economic efficiency.
Firstly, the concept of social time preference reflects the view that the market rate of interest does not accurately reflect society's preference for present as opposed to future consumption, and that a discount rate based on a social time preference rate should be used to calculate NPVs from a public interest viewpoint. For reasons which will be discussed below, the social time preference rate is usually judged to be lower than the market rate of interest.
Secondly, the concept of social opportunity cost is based on the notion that, because of tax-induced distortions to the pattern of resource allocation, the opportunity cost to the economy of raising public funds for government expenditures is higher than the nominal amount raised. This suggests that a public project should have a present value of benefits sufficiently large not only to offset project costs (the NPV>0 rule), but also to offset the premium on the cost of public funds if the project is to make a net contribution to efficiency.
Thirdly, the fact that a project has a NPV>0 does not necessarily imply that now is the most efficient time to implement it. Because additional information about the project variables - prices, costs etc. - may accrue in the future there could be an advantage to keeping open the option of undertaking the project.
If benefit-cost analysis is to assist in the decision-making process the analysis must be conducted in advance of the project being undertaken. This means that the value of none of the variables involved in the analysis can be observed, but rather has to be predicted. Risk and uncertainty are always associated with predictions about the future and should be taken into account in the benefit-cost analysis. Since risk and uncertainty impose costs on decisionmakers, these costs need to be assessed and measures taken to reduce them if possible. One way of reducing risk and uncertainty is to acquire additional information mdash; what a benefit-cost analysis does mdash; and the value of information is briefly discussed in Chapter 10. The present Chapter discusses the related concepts of risk and uncertainty.
Risk and Uncertainty
In the preceding Chapters, exercises and case studies we have assumed that all costs and benefits to be included in a cash flow are known with certainty. While this assumption might be acceptable in the context of project evaluation where the analyst is undertaking an ex post assessment of what has already occurred, it is clearly an unrealistic assumption to make where the purpose of the analysis is to undertake an appraisal of proposed projects where one has to forecast future cost and benefit flows. The future is uncertain: we do not know with certainty what the future values of a project's costs and benefits will be.
A large project, such as construction of a major highway or development of a large mine, will have a significant impact on the economy. The spending in the construction and operating phases will generate income and employment, and public sector decision-makers often take these effects into account in deciding whether or not to undertake the project. An economic impact analysis is a different procedure from a cost-benefit analysis in that it attempts to predict, but not evaluate, the effects of a project. Since the data assembled in the course of a cost-benefit analysis are often used as inputs to an economic impact analysis the two types of analyses tend to become related in the minds of decision-makers and may be undertaken by the same group of analysts.
In this Chapter we survey briefly three approaches to economic impact analysis: the income multiplier approach; the inter-industry model; and the computable general equilibrium model. Use of the latter two approaches involves a degree of technical expertise and would generally not be undertaken by the non-specialist. In discussing economic impacts we emphasize that these are not the same as the costs or benefits measured by a cost-benefit analysis. However there may be costs and benefits associated with the project's economic impact and the decision-maker may wish to take these into account.
The decision whether or not to take the multiplier or flow-on effects into account in the evaluation should be based on an assessment of the extent to which similar such effects would or would not occur in the absence of the project in question.