An empirical investigation of intuitions about uptake

Since Austin’s introduction of the locutionary-illocutionary-perlocutionary distinction, it has been a matter of debate within speech act theory whether illocutionary acts like promising, warning, refusing and telling require audience ‘uptake’ in order to be performed. Philosophers on different sides of this debate have tried to support their positions by appealing to hypothetical scenarios, designed to elicit intuitive judgements about the role of uptake. However, philosophers’ intuitions appeared to remain deadlocked, while laypeople’s intuitions have not yet been probed. To begin rectifying that, we ran two experiments probing lay intuitions about the implications of uptake failure. Overall, we found that participants’ responses were skewed towards agreement that speech acts were performed, despite the lack of uptake. There were, however, significant differences across the four different speech act types we investigated (with the highest levels of agreement found for refusing, followed by warning, then telling, and finally promising). We also obtained evidence of complex effects relating to the (high or low) stakes involved in the scenarios. While this study only represents an initial exploration of intuitions about uptake, our results form a basis for further research into their nature and significance, across a range of speech acts, scenarios, and experimental designs

Modulation of Global Low-Frequency Motions Underlies Allosteric Regulation: Demonstration in CRP/FNR Family Transcription Factors

Allostery is a fundamental process by which ligand binding to a protein alters its activity at a distinct site. There is growing evidence that allosteric cooperativity can be communicated by modulation of protein dynamics without conformational change. The mechanisms, however, for communicating dynamic fluctuations between sites are debated. We provide a foundational theory for how allostery can occur as a function of low-frequency dynamics without a change in structure. We have generated coarse-grained models that describe the protein backbone motions of the CRP/FNR family transcription factors, CAP of Escherichia coli and GlxR of Corynebacterium glutamicum. The latter we demonstrate as a new exemplar for allostery without conformation change. We observe that binding the first molecule of cAMP ligand is correlated with modulation of the global normal modes and negative cooperativity for binding the second cAMP ligand without a change in mean structure. The theory makes key experimental predictions that are tested through an analysis of variant proteins by structural biology and isothermal calorimetry. Quantifying allostery as a free energy landscape revealed a protein ‘‘design space’’ that identified the inter- and intramolecular regulatory parameters that frame CRP/FNR family allostery. Furthermore, through analyzing CAP variants from diverse species, we demonstrate an evolutionary selection pressure to conserve residues crucial for allosteric control. This finding provides a link between the position of CRP/FNR transcription factors within the allosteric free energy landscapes and evolutionary selection pressures. Our study therefore reveals significant features of the mechanistic basis for allostery. Changes in low-frequency dynamics correlate with allosteric effects on ligand binding without the requirement for a defined spatial pathway. In addition to evolving suitable three-dimensional structures, CRP/FNR family transcription factors have been selected to occupy a dynamic space that fine-tunes biological activity and thus establishes the means to engineer allosteric mechanisms driven by low-frequency dynamics

When chefs adopt a school? An evaluation of a cooking intervention in English primary schools

This article sets out the findings from research on the impact of a, UK based, chefs in schools teaching programme on food, health, nutrition and cookery. Professional chefs link with local schools, where they deliver up to three sessions to one class over a year. The research measured the impact of a standardised intervention package and changes in food preparation and consumption as well as measuring cooking confidence. The target group was 9–11 year olds in four schools. The main data collection method was a questionnaire delivered 2 weeks before the intervention and 2 weeks afterwards. There was a group of four matched control schools. Those taking part in the intervention were enthused and engaged by the sessions and the impact measures indicated an intention to change. There were gains in skills and confidence to prepare and ask for the ingredients to be purchased for use in the home. Following the session with the chef, the average reported cooking confidence score increased from 3.09 to 3.35 (by 0.26 points) in the intervention group – a statistically significant improvement. In the control group this change was not statistically significant. Children’s average reported vegetable consumption increased after the session with the chef, with the consumption score increasing from 2.24 to 2.46 points (0.22 points) again, a statistically significant increase with no significant changes in the control group. The research highlights the need to incorporate evaluation into school cooking initiatives as the findings can provide valuable information necessary to fine-tune interventions and to ensure consistency of the healthy eating messages

Phase transition and hyperscaling violation for scalar Black Branes

We investigate the thermodynamical behavior and the scaling symmetries of the scalar dressed black brane (BB) solutions of a recently proposed, exactly integrable Einstein-scalar gravity model [1], which also arises as compactification of (p-1)-branes with a smeared charge. The extremal, zero temperature, solution is a scalar soliton interpolating between a conformal invariant AdS vacuum in the near-horizon region and a scale covariant metric (generating hyperscaling violation on the boundary field theory) asymptotically. We show explicitly that for the boundary field theory this implies the emergence of an UV length scale (related to the size of the brane), which decouples in the IR, where conformal invariance is restored. We also show that at high temperatures the system undergoes a phase transition. Whereas at small temperature the Schwarzschild-AdS BB is stable, above a critical temperature the scale covariant, scalar-dressed BB solution, becomes energetically preferred. We calculate the critical exponent z and the hyperscaling violation parameter of the scalar-dressed phase. In particular we show that the hyperscaling violation parameter is always negative. We also show that the above features are not a peculiarity of the exact integrable model of Ref.[1], but are a quite generic feature of Einstein-scalar and Einstein-Maxwell-scalar gravity models for which the squared-mass of the scalar field is positive and the potential vanishes exponentially as the scalar field goes to minus infinity.Comment: 20 pages, 4 figures. In the revised version it has been pointed out that the Einstein-scalar gravity model considered in the paper also arises as compactification of black p-branes with smeared charge

Pathologies in Asymptotically Lifshitz Spacetimes

There has been significant interest in the last several years in studying possible gravitational duals, known as Lifshitz spacetimes, to anisotropically scaling field theories by adding matter to distort the asymptotics of an AdS spacetime. We point out that putative ground state for the most heavily studied example of such a spacetime, that with a flat spatial section, suffers from a naked singularity and further point out this singularity is not resolvable by any known stringy effect. We review the reasons one might worry that asymptotically Lifshitz spacetimes are unstable and employ the initial data problem to study the stability of such systems. Rather surprisingly this question, and even the initial value problem itself, for these spacetimes turns out to generically not be well-posed. A generic normalizable state will evolve in such a way to violate Lifshitz asymptotics in finite time. Conversely, enforcing the desired asymptotics at all times puts strong restrictions not just on the metric and fields in the asymptotic region but in the deep interior as well. Generically, even perturbations of the matter field of compact support are not compatible with the desired asymptotics.Comment: 36 pages, 1 figure, v2: Enhanced discussion of singularity, including relationship to Gubser's conjecture and singularity in RG flow solution, plus minor clarification

Poloxomer 188 Has a Deleterious Effect on Dystrophic Skeletal Muscle Function

Duchenne muscular dystrophy (DMD) is an X-linked, fatal muscle wasting disease for which there is currently no cure and limited palliative treatments. Poloxomer 188 (P188) is a tri-block copolymer that has been proposed as a potential treatment for cardiomyopathy in DMD patients. Despite the reported beneficial effects of P188 on dystrophic cardiac muscle function, the effects of P188 on dystrophic skeletal muscle function are relatively unknown. Mdx mice were injected intraperitoneally with 460 mg/kg or 30 mg/kg P188 dissolved in saline, or saline alone (control). The effect of single-dose and 2-week daily treatment was assessed using a muscle function test on the Tibialis Anterior (TA) muscle in situ in anaesthetised mice. The test comprises a warm up, measurement of the force-frequency relationship and a series of eccentric contractions with a 10% stretch that have previously been shown to cause a drop in maximum force in mdx mice. After 2 weeks of P188 treatment at either 30 or 460 mg/kg/day the drop in maximum force produced following eccentric contractions was significantly greater than that seen in saline treated control mice (P = 0.0001). Two week P188 treatment at either dose did not significantly change the force-frequency relationship or maximum isometric specific force produced by the TA muscle. In conclusion P188 treatment increases susceptibility to contraction-induced injury following eccentric contractions in dystrophic skeletal muscle and hence its suitability as a potential therapeutic for DMD should be reconsidered

Choice of geographic unit influences socioeconomic inequalities in breast cancer survival

Socioeconomic differences in age-standardised crude survival for women diagnosed with breast cancer during 1991–1999 in England were influenced by the population of the geographic area used to assign the deprivation index, but not by the choice of index

Area-level deprivation and adiposity in children: is the relationship linear?

OBJECTIVE: It has been suggested that childhood obesity is inversely associated with deprivation, such that the prevalence is higher in more deprived groups. However, comparatively few studies actually use an area-level measure of deprivation, limiting the scope to assess trends in the association with obesity for this indicator. Furthermore, most assume a linear relationship. Therefore, the aim of this study was to investigate associations between area-level deprivation and three measures of adiposity in children: body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR). DESIGN: This is a cross-sectional study in which data were collected on three occasions a year apart (2005-2007). SUBJECTS: Data were available for 13,333 children, typically aged 11-12 years, from 37 schools and 542 lower super-output areas (LSOAs). MEASURES: Stature, mass and WC. Obesity was defined as a BMI and WC exceeding the 95th centile according to British reference data. WHtR exceeding 0.5 defined obesity. The Index of Multiple Deprivation affecting children (IDACI) was used to determine area-level deprivation. RESULTS: Considerable differences in the prevalence of obesity exist between the three different measures. However, for all measures of adiposity the highest probability of being classified as obese is in the middle of the IDACI range. This relationship is more marked in girls, such that the probability of being obese for girls living in areas at the two extremes of deprivation is around half that at the peak, occurring in the middle. CONCLUSION: These data confirm the high prevalence of obesity in children and suggest that the relationship between obesity and residential area-level deprivation is not linear. This is contrary to the 'deprivation theory' and questions the current understanding and interpretation of the relationship between obesity and deprivation in children. These results could help make informed decisions at the local level

Dynamics of direct inter-pack encounters in endangered African wild dogs

Aggressive encounters may have important life history consequences due to the potential for injury and death, disease transmission, dispersal opportunities or exclusion from key areas of the home range. Despite this, little is known of their detailed dynamics, mainly due to the difficulties of directly observing encounters in detail. Here, we describe detailed spatial dynamics of inter-pack encounters in African wild dogs (Lycaon pictus), using data from custom-built high-resolution GPS collars in 11 free-ranging packs. On average, each pack encountered another pack approximately every 7 weeks and met each neighbour twice each year. Surprisingly, intruders were more likely to win encounters (winning 78.6% of encounters by remaining closer to the site in the short term). However, intruders did tend to move farther than residents toward their own range core in the short-term (1 h) post-encounter, and if this were used to indicate losing an encounter, then the majority (73.3%) of encounters were won by residents. Surprisingly, relative pack size had little effect on encounter outcome, and injuries were rare (<15% of encounters). These results highlight the difficulty of remotely scoring encounters involving mobile participants away from static defendable food resources. Although inter-pack range overlap was reduced following an encounter, encounter outcome did not seem to drive this, as both packs shifted their ranges post-encounter. Our results indicate that inter-pack encounters may be lower risk than previously suggested and do not appear to influence long-term movement and ranging

Increasing condom use in heterosexual men: development of a theory-based interactive digital intervention

Increasing condom use to prevent sexually transmitted infections is a key public health goal. Interventions are more likely to be effective if they are theory- and evidence-based. The Behaviour Change Wheel (BCW) provides a framework for intervention development. To provide an example of how the BCW was used to develop an intervention to increase condom use in heterosexual men (the MenSS website), the steps of the BCW intervention development process were followed, incorporating evidence from the research literature and views of experts and the target population. Capability (e.g. knowledge) and motivation (e.g. beliefs about pleasure) were identified as important targets of the intervention. We devised ways to address each intervention target, including selecting interactive features and behaviour change techniques. The BCW provides a useful framework for integrating sources of evidence to inform intervention content and deciding which influences on behaviour to target