Young people's participation in the development of a self-care intervention--a multi-site formative research study.

The poor outcomes of young people with chronic health conditions indicate that current services and self-care programmes are not meeting the needs of young people. How young people self-manage their condition impacts on long-term health outcomes, but there is little published evidence that details the development of self-care programmes and their most effective components. This article reports on an innovative formative research study, the purpose of which was to develop a self-care intervention prototype. Participants were 87 young people, aged 12-17, and seven young adult facilitators, aged 18-25, with type 1 diabetes or asthma. Each contributed to talking groups exploring themes that young people wanted to be addressed within a self-care programme. Instead of being focused on 'illness', young people's main concerns were directed toward 'life as an adolescent', while at the same time building sustainable daily routines of self-care. Overall, this article illustrates the process of initiating and implementing a developmental approach focused on young people, while also demonstrating the tailored self-care intervention that the process developed. This approach can be used to involve young people in the design and development of other conditions that rely on self-care interventions

Semantics and the stratification of explanation in cognitive science

This work is concerned with a pervasive problem in Cognitive Science which I have called the "stratificational" approach. I argue that the division into "levels of explanation" that runs as a constant theme through much work in Cognitive Science and in particular natural language semantics, is in direct conflict with neuroscientific evidence. I claim it is also in conflict with a right understanding of the philosophical notion of "evidence". The neuroscientific work is linked with the philosophical problem to provide a critique of concrete cases of research within the natural language semantics community. More recent neuroscientifically aware research is examined and it is demonstrated that it suffers similar problems due to the same deep running assumptions as those which effect traditional formalist theory. The contribution of this thesis is thought to be that of a demonstration of the essential nature and indeed the ubiquity of the basic assumptions in the field. Also, a new link is forged between the concerns of the formalists and certain seemingly more abstract philosophical work. This link enables us to see how much philosophical problems infect research into cognition and language. It is argued that practical research in Cognitive Science simply cannot be seen to be independent of the philosophical basis of the entire subject. The resulting picture of Cognitive Science and its place is outlined and explored with special emphasis on what I have called the "Principle of Semantic Indistinguishabliity" which says that the contribution of what can be broadly termed "environment" is epitemologically opaque to our cognition. The importance of this principle is discussed.The purpose of this work is to draw out a fundamental thread of reasoning and methodology that underlies most traditional work, and some not so traditional work, in Cognitive Science. It will be argued that this line of reasoning is at odds with the implications of modern neuroscience and cannot base a reasonable claim to "explain" human cognition. The picture I shall identify is that which I shall call "stratified". This, in general, is an attempt at explanation that divides into "levels of explanation", each with its own concepts that are said to be essential to the explanation of a phenomenon. There are specific and pragmatic manifestations of this, I discuss these in Chapter 3 and 7 in particular. There are also more abstract expressions of the same tendency which I examine mainly in Chapter 6. One of the principle tasks is to demonstrate the links between the assumptions of the more abstract formulations of this approach and th eir pragmatic instantiations in work in Cognitive Science. This allows it to be made clear that certain methodological problems are ubiquitous within the field and are not simply a result of the particular pragmatics of a particular research area.In Cognitive Science as a whole, it is generally appreciated today that there are problems to do with integration of traditional formal systems and the evolutionary and biological aspects of human cognition. One aim of this work is exactly to give an argument, supported from work in the brain sciences, that a certain methodology - particularly that enshrined within formal systems in language semantics - is strongly denied its evidential basis as a result of certain empirical considerations. It is also denied much of its basis as a result of the incongruity between the original motivations of logical formalism and the use to which this formalism is put today. The conclusion of this is that Cognitive Science's role in certain areas is severely limited and it crucially relies on an amount of empirical brain research in places thought usually to be completely separate from the "low-level" evidence from neuroscience. Part of my thesis is that stratified systems and particularly systems of formal logic within linguistics and semantics, cannot possibly be independent in the way imagined. There is also exploration of a general point regarding the character of the relation between strata in a stratified theory. There is, I shall argue, an irresolvable tension between the desire to have separate strata which are both independent but related. We shall see this both in concrete terms in the discussion of Fodor and in the abstract in the discussion of McDowell.George Lakoffhas expressed agreement with this particular premise: " ... linguistic results ... indicate that human reason uses some of the same mechanisms involved in perception and ... human reason can be seen as growing out of perceptual and motor mechanisms."1If this is correct, then I think that there are enormous implications for Cognitive Science in its practise of semantics since the mechanisms of motor and perceptual systems impose radical constraints when applied in the area of semantics.Given this, my aim is to demonstrate that certain seemingly theoryindependent areas of research in Cognitive Science such as linguistics and natural language semantics are actually infected with damaging assumptions from certain misguided philosophical positions. The idea that we can simply model things in Cognitive Science and wait for someone else to sort out the theoretical structure into which all of the models will fit is not tenable. I shall demonstrate this in several concrete cases and couple this with a critique from neuroscience which is crucially related to a more philosophical critique of fundamental assumptions. The structure of the work is as follows. Firstly, I give an overview of foundational issues in Cognitive Science by discussing central works. Then, I introduce the main problems in concrete form by way of an examination of certain approaches to inference in formal semantics. Chapter 4 expands on this in an analysis of the notion of "compositionality" with reference to the "stratificational" approach I find apparent in traditional work in Cognitive Science and the assumptions it disguises. Chapter 5 introduces the themes from neuroscience and the relations they have to the philosophical critique in Chapter 6. In Chapter 7, I demonstrate that the assumptions I have identified are present even in work motivated by a desire to leave behind the formalist program. I explain why this is the case and the implications this has for a correct view of "evidence" in Cognitive Science. At this point, I deal with pertinent objections to my view stemming from the parts of the discipline I have mentioned. Chapter 8 condenses the problem and shows the fundamentals of the whole problem in relief, suggesting what all of the preceding means for Cognitive Science

The effect of one-session exposure treatment on selective processing and explicit memory bias in snake- and spider-fearful participants

Unlike the empirically supported phenomenon of anxiety-induced selective processing bias, research on congruent explicit memory bias is inconclusive; indeed, there is evidence for recall decrements of threat-relevant information. There is also a paucity of literature examining the effects of treatment on these cognitive biases. Thus, the purpose of this study was to examine the effect of exposure treatment on selective processing and explicit memory bias in snake- and spider-fearful participants by measuring implicit and explicit memory for central and peripheral environmental details. Recall for environmental details in a fearful group that received treatment was compared to a fearful group that did not receive treatment and to a non-fearful control group to evaluate the presence of selective processing bias, explicit memory bias, and the effect of treatment on these phenomena. Results indicated no implicit or explicit memory biases in any participant group. There was, however, the presence of significant memory deficits, specifically for peripheral details, in fearful participants who did not receive treatment

Changes in intergenerational eating patterns and the impact on childhood obesity

The objective of this study was to examine intergenerational eating patterns within two sets of families, those with an obese child and those with a normal weight child, and to assess the impact of intergenerational influences on children's eating. A qualitative study design was used, incorporating focus groups and semi-structured interviews. Sixteen focus groups took place and 27 semi-structured interviews were held with different generations. Focus groups were conducted in the community with grandparents, parents and children from different families. This was followed by semi-structured interviews, involving individuals from three generations within families with an obese child and within families with a normal weight child. An examination of intergenerational eating has shown that eating patterns have changed regardless of whether or not families have children who are obese. The grandparent's eating patterns were more structured, whereas the children's eating patterns were less so. There have been more changes, and eating is less structured, within those families with an obese child than those families with a normal weight child. It is recommended that approaches to tackling childhood obesity concentrate on the family setting and the ways in which professionals can support families to change eating practices. Future research should formally test the relationship between the concept 'structured eating' and the 'what' of eating, in order to determine whether there is a link between intergenerational eating patterns and childhood obesity. © The Author(s) 2010

Direct entry by RNase E is a major pathway for the degradation and processing of RNA in Escherichia coli

Escherichia coli endoribonuclease E has a major influence on gene expression. It is essential for the maturation of ribosomal and transfer RNA as well as the rapid degradation of messenger RNA. The latter ensures that translation closely follows programming at the level of transcription. Recently, one of the hallmarks of RNase E, i.e. its ability to bind via a 5'-monophosphorylated end, was shown to be unnecessary for the initial cleavage of some polycistronic tRNA precursors. Here we show using RNA-seq analyses of ribonuclease-deficient strains in vivo and a 5'-sensor mutant of RNase E in vitro that, contrary to current models, 5'-monophosphate-independent, 'direct entry' cleavage is a major pathway for degrading and processing RNA. Moreover, we present further evidence that direct entry is facilitated by RNase E binding simultaneously to multiple unpaired regions. These simple requirements may maximize the rate of degradation and processing by permitting multiple sites to be surveyed directly without being constrained by 5'-end tethering. Cleavage was detected at a multitude of sites previously undescribed for RNase E, including ones that regulate the activity and specificity of ribosomes. A potentially broad role for RNase G, an RNase E paralogue, in the trimming of 5'-monophosphorylated ends was also revealed

The recognition of structured elements by a conserved groove distant from domains associated with catalysis is an essential determinant of RNase E

RNase E is an endoribonuclease found in many bacteria, including important human pathogens. Within Escherichia coli, it has been shown to have a major role in both the maturation of all classes of RNA involved in translation and the initiation of mRNA degradation. Thus, knowledge of the major determinants of RNase E cleavage is central to our understanding and manipulation of bacterial gene expression. We show here that the binding of RNase E to structured RNA elements is crucial for the processing of tRNA, can activate catalysis and may be important in mRNA degradation. The recognition of structured elements by RNase E is mediated by a recently discovered groove that is distant from the domains associated with catalysis. The functioning of this groove is shown here to be essential for E. coli cell viability and may represent a key point of evolutionary divergence from the paralogous RNase G family, which we show lack amino acid residues conserved within the RNA-binding groove of members of the RNase E family. Overall, this work provides new insights into the recognition and cleavage of RNA by RNase E and provides further understanding of the basis of RNase E essentiality in E. coli

Transient silencing of antibiotic resistance by mutation represents a significant potential source of unanticipated therapeutic failure

Sporadic literature reports describe isolates of pathogenic bacteria that harbor an antibiotic resistance determinant but remain susceptible to the corresponding antibiotic as a consequence of a genetic defect. Such strains represent a source from which antibiotic resistance may reemerge to cause treatment failure in patients. Here, we report a systematic investigation into the prevalence and nature of this phenomenon, which we term silencing of antibiotic resistance by mutation (SARM). Instances of SARM were detected among 1,470 Staphylococcus aureus isolates through side-by-side comparison of antibiotic resistance genotype (as determined by whole-genome sequencing) versus phenotype (as assessed through susceptibility testing). Of the isolates analyzed, 152 (10.3%) harbored a silenced resistance gene, including 46 (3.1%) that exhibited SARM to currently deployed antistaphylococcal drugs. SARM resulted from diverse mutational events but most commonly through frameshift mutation of resistance determinants as a result of point deletion in poly(A) tracts. The majority (∼90%) of SARM strains reverted to antibiotic resistance at frequencies of ≥10−9; thus, while appearing antibiotic sensitive in the clinical microbiology laboratory, most S. aureus isolates exhibiting SARM will revert to antibiotic resistance at frequencies achievable in patients. In view of its prevalence in a major pathogen, SARM represents a significant potential threat to the therapeutic efficacy of antibiotics

Resistance to antibacterial antifolates in multidrug-resistant Staphylococcus aureus: prevalence estimates and genetic basis

Objectives Antibacterial antifolate drugs might have a wider role in the management of staphylococcal infection. One factor that could potentially limit their use in this context is pre-existing resistance. Here we explored the prevalence and genetic basis for resistance to these drugs in a large collection (n = 1470) of multidrug-resistant (MDR) Staphylococcus aureus. Methods Strains were subjected to susceptibility testing to detect resistance to trimethoprim, sulfamethoxazole, co-trimoxazole and the investigational drug, iclaprim. Whole-genome sequences were interrogated to establish the genetic basis for resistance. Results According to CLSI breakpoints, 15.2% of the strains were resistant to trimethoprim, 5.2% to sulfamethoxazole and 4.1% to co-trimoxazole. Using the proposed breakpoint for iclaprim, 89% of the trimethoprim-resistant strains exhibited non-susceptibility to this agent. Sulfamethozaxole resistance was exclusively the result of mutation in the drug target (dihydropteroate synthase). Resistance to trimethoprim and iclaprim also resulted from mutation in the target (dihydrofolate reductase; DHFR) but was more commonly associated with horizontal acquisition of genes encoding drug-insensitive DHFR proteins. Among the latter, we identified a novel gene (dfrL) encoding a DHFR with ∼35% identity to native and known resistant DHFRs, which was confirmed via molecular cloning to mediate high-level resistance. Conclusions This study provides a detailed picture of the genotypes underlying staphylococcal resistance to antifolate drugs in clinical use and in development. Prevalence estimates suggest that resistance to the diaminopyrimidines (trimethoprim/iclaprim) is not uncommon among MDR S. aureus, and considerably higher than observed for sulfamethoxazole or co-trimoxazole

How children eat may contribute to rising levels of obesity children's eating behaviours: An intergenerational study of family influences

The term ‘obesogenic environment’ is rapidly becoming part of common phraseology. However, the influence of the family and the home environment on children's eating behaviours is little understood. Research that explores the impact of this micro environment and intergenerational influences affecting children's eating behaviours is long overdue. A qualitative, grounded theory approach, incorporating focus groups and semi-structured interviews, was used to investigate the family environment and specifically, the food culture of different generations within families. What emerged was a substantive theory based on ‘ordering of eating’ that explains differences in eating behaviours within and between families. Whereas at one time family eating was highly ordered and structured, typified by the grandparent generation, nowadays family eating behaviours are more haphazard and less ordered, evidenced by the way the current generation of children eat. Most importantly, in families with an obese child eating is less ordered compared with those families with a normal weight child. Ordering of eating' is a unique concept to emerge. It shows that an understanding of the eating process is crucial to the development and improvement of interventions targeted at addressing childhood obesity within the family context

Rapid cleavage of RNA by RNase E in the absence of 5′ monophosphate stimulation

The best characterized pathway for the initiation of mRNA degradation in Escherichia coli involves the removal of the 5′‐terminal pyrophosphate to generate a monophosphate group that stimulates endonucleolytic cleavage by RNase E. We show here however, using well‐characterized oligonucleotide substrates and mRNA transcripts, that RNase E can cleave certain RNAs rapidly without requiring a 5′‐monophosphorylated end. Moreover, the minimum substrate requirement for this mode of cleavage, which can be categorized as ‘direct’ or ‘internal’ entry, appears to be multiple single‐stranded segments in a conformational context that allows their simultaneous interaction with RNase E. While previous work has alluded to the existence of a 5′ end‐independent mechanism of mRNA degradation, the relative simplicity of the requirements identified here for direct entry suggests that it could represent a major means by which mRNA degradation is initiated in E. coli and other organisms that contain homologues of RNase E. Our results have implications for the interplay of translation and mRNA degradation and models of gene regulation by small non‐coding RNAs