Comprehensive evaluation of genetic variation in S100A7 suggests an association with the occurrence of allergic rhinitis

<p>Abstract</p> <p>Background</p> <p>S100A7 is a calcium-binding protein with chemotactic and antimicrobial properties. S100A7 protein levels are decreased in nasal lavage fluid from individuals with ongoing allergic rhinitis, suggesting a role for S100A7 in allergic airway inflammation. The aims of this study were to describe genetic variation in <it>S100A7 </it>and search for associations between this variation and allergic rhinitis.</p> <p>Methods</p> <p>Peripheral blood was collected from 184 atopic patients with a history of pollen-induced allergic rhinitis and 378 non-atopic individuals, all of Swedish origin. DNA was extracted and the <it>S100A7 </it>gene was resequenced in a subset of 47 randomly selected atopic individuals. Nine polymorphisms were genotyped in 184 atopic and 378 non-atopic individuals and subsequently investigated for associations with allergic rhinitis as well as skin prick test results. Haplotypes were estimated and compared in the two groups.</p> <p>Results</p> <p>Thirteen polymorphisms were identified in <it>S100A7</it>, of which 7 were previously undescribed. rs3014837 (G/C), which gives rise to an Asp → Glu amino acid shift, had significantly increased minor allele frequency in atopic individuals. The major haplotype, containing the major allele at all sites, was more common in non-atopic individuals, while the haplotype containing the minor allele at rs3014837 was equally more common among the atopic individuals. Additionally, heterozygotes at this site had significantly higher scores in skin prick tests for 9 out of 11 tested allergens, compared to homozygotes.</p> <p>Conclusion</p> <p>This is the first study describing genetic variation, associated with allergy, in <it>S100A7</it>. The results indicate that rs3014837 is linked to allergic rhinitis in our Swedish population and render S100A7 a strong candidate for further investigations regarding its role in allergic inflammation.</p

Implementation of a workplace smoking ban in bars: The limits of local discretion

<p>Abstract</p> <p>Background</p> <p>In January 1998, the California state legislature extended a workplace smoking ban to bars. The purpose of this study was to explore the conditions that facilitate or hinder compliance with a smoking ban in bars.</p> <p>Methods</p> <p>We studied the implementation of the smoking ban in bars by interviewing three sets of policy participants: bar employers responsible for complying with the law; local government officials responsible for enforcing the law; and tobacco control activists who facilitated implementation. We transcribed the interviews and did a qualitative analysis of the text.</p> <p>Results</p> <p>The conditions that facilitated bar owners' compliance with a smoking ban in bars included: if the cost to comply was minimal; if the bars with which they were in competition were in compliance with the smoking ban; and if there was authoritative, consistent, coordinated, and uniform enforcement. Conversely, the conditions that hindered compliance included: if the law had minimal sanctions; if competing bars in the area allowed smoking; and if enforcement was delayed or inadequate.</p> <p>Conclusion</p> <p>Many local enforcers wished to forfeit their local discretion and believed the workplace smoking ban in bars would be best implemented by a state agency. The potential implication of this study is that, given the complex nature of local politics, smoking bans in bars are best implemented at a broader provincial or national level.</p

The motivational drive to natural rewards is modulated by prenatal glucocorticoid exposure

Exposure to elevated levels of glucocorticoids (GCs) during neurodevelopment has been identified as a triggering factor for the development of reward-associated disorders in adulthood. Disturbances in the neural networks responsible for the complex processes that assign value to rewards and associated stimuli are critical for disorders such as depression, obsessive–compulsive disorders, obesity and addiction. Essential in the understanding on how cues influence behavior is the Pavlovian–instrumental transfer (PIT), a phenomenon that refers to the capacity of a Pavlovian stimulus that predicts a reward to elicit instrumental responses for that same reward. Here, we demonstrate that in utero exposure to GCs (iuGC) impairs both general and selective versions of the PIT paradigm, suggestive of deficits in motivational drive. The iuGC animals presented impaired neuronal activation pattern upon PIT performance in cortical and limbic regions, as well as morphometric changes and reduced levels of dopamine in prefrontal and orbitofrontal cortices, key regions involved in the integration of Pavlovian and instrumental stimuli. Normalization of dopamine levels rescued this behavior, a process that relied on D2/D3, but not D1, dopamine receptor activation. In summary, iuGC exposure programs the mesocorticolimbic dopaminergic circuitry, leading to a reduction in the attribution of the incentive salience to cues, in a dopamine-D2/D3-dependent manner. Ultimately, these results are important to understand how GCs bias incentive processes, a fact that is particularly relevant for disorders where differential attribution of incentive salience is critical.We thank Pedro Morgado for discussions and help in the technical aspects of PIT procedure. This project was supported by a grant of Institute for the Study of Affective Neuroscience (ISAN) and by Janssen Neuroscience Prize. CS-C, SB, MMC and AJR are recipients of Fundacao para a Ciencia e Tecnologia (FCT) fellowships (CS-C: SFRH/BD/51992/2012; SB: SFRH/BD/89936/2012; MMC: SRFH/BD/51061/2010; AJR: SFRH/BPD/33611/2009)

Understanding the everyday designer in organisations

This paper builds upon the existing concept of an everyday designer as a non-expert designer who carries out design activities using available resources in a given environment. It does so by examining the design activities undertaken by non-expert, informal, designers in organisations who make use of the formal and informal technology already in use in organisations while designing to direct, influence, change or transform the practices of people in the organisation. These people represent a cohort of designers who are given little attention in the literature on information systems, despite their central role in the formation of practice and enactment of technology in organisations. The paper describes the experiences of 18 everyday designers in an academic setting using three concepts: everyday designer in an organisation, empathy through design and experiencing an awareness gap. These concepts were constructed through the analysis of in-depth interviews with the participants. The paper concludes with a call for tool support for everyday designers in organisations to enable them to better understand the audience for whom they are designing and the role technology plays in the organisation

Discovery of Prostamide F2α and Its Role in Inflammatory Pain and Dorsal Horn Nociceptive Neuron Hyperexcitability

It was suggested that endocannabinoids are metabolized by cyclooxygenase (COX)-2 in the spinal cord of rats with kaolin/λ-carrageenan-induced knee inflammation, and that this mechanism contributes to the analgesic effects of COX-2 inhibitors in this experimental model. We report the development of a specific method for the identification of endocannabinoid COX-2 metabolites, its application to measure the levels of these compounds in tissues, and the finding of prostamide F2α (PMF2α) in mice with knee inflammation. Whereas the levels of spinal endocannabinoids were not significantly altered by kaolin/λ-carrageenan-induced knee inflammation, those of the COX-2 metabolite of AEA, PMF2α, were strongly elevated. The formation of PMF2α was reduced by indomethacin (a non-selective COX inhibitor), NS-398 (a selective COX-2 inhibitor) and SC-560 (a selective COX-1 inhibitor). In healthy mice, spinal application of PMF2α increased the firing of nociceptive (NS) neurons, and correspondingly reduced the threshold of paw withdrawal latency (PWL). These effects were attenuated by the PMF2α receptor antagonist AGN211336, but not by the FP receptor antagonist AL8810. Also prostaglandin F2α increased NS neuron firing and reduced the threshold of PWL in healthy mice, and these effects were antagonized by AL8810, and not by AGN211336. In mice with kaolin/λ-carrageenan-induced knee inflammation, AGN211336, but not AL8810, reduced the inflammation-induced NS neuron firing and reduction of PWL. These findings suggest that inflammation-induced, and prostanoid-mediated, enhancement of dorsal horn NS neuron firing stimulates the production of spinal PMF2α, which in turn contributes to further NS neuron firing and pain transmission by activating specific receptors

Risk stratification of childhood cancer survivors necessary for evidence-based clinical long-term follow-up

Background: Reorganisation of clinical follow-up care in England was proposed by the National Cancer Survivorship Initiative (NCSI), based on cancer type and treatment, ranging from Level 1 (supported self-management) to Level 3 (consultant-led care). The objective of this study was to provide an investigation of the risks of serious adverse health-outcomes associated with NCSI Levels of clinical care using a large population-based cohort of childhood cancer survivors. Methods: The British Childhood Cancer Survivor Study (BCCSS) was used to investigate risks of specific causes of death, subsequent primary neoplasms (SPNs) and non-fatal non-neoplastic outcomes by NCSI Level. Results: Cumulative (excess) risks of specified adverse outcomes by 45 years from diagnosis among non-leukaemic survivors assigned to NCSI Levels 1, 2 and 3 were for: SPNs—5% (two-fold expected), 14% (four-fold expected) and 21% (eight-fold expected); non-neoplastic death—2% (two-fold expected), 4% (three-fold expected) and 8% (seven-fold expected); non-fatal non-neoplastic condition—14%, 27% and 40%, respectively. Consequently overall cumulative risks of any adverse health outcome were 21%, 45% and 69%, respectively. Conclusions: Despite its simplicity the risk stratification tool provides clear and strong discrimination between survivors assigned to different NCSI Levels in terms of long-term cumulative and excess risks of serious adverse outcomes

A conceptual classification of parents’ attributions of the role of food advertising in children’s diets

Background: High levels of child obesity are triggering growing concerns about the prevalence and effects of food advertising targeted at children. Efforts to address this advertising are confounded by the expanding repertoire of media and promotional techniques used to reach and attract children. The present study explored parents’ views on food marketing and the strategies parents employ when attempting to ameliorate its effects. As part of an online survey of Australian parents’ attitudes towards a range of food advertisements, respondents were invited to provide additional comment in an open-ended question. The question was optional and asked “Are there any other comments you would like to make?”. One in five of the survey respondents (18%; n = 235) elected to answer this question by discussing their views on food advertising and children’s diets. The responses were imported into NVivo10 for coding and analysis. A grounded approach was used to draw meaning from the data and develop a proposed conceptual classification of parents’ attributions relating to food advertising and its consequences.Results: The majority of responses related to the negative perceived effects of unhealthy food advertising on children’s diets, with few respondents considering such advertisements to be innocuous. The responses were classified into four conceptual categories reflecting differing attitudes to advertising (negative to neutral) and varying levels of locus of control (low to high). The typical characteristics of parents allocated to the four categories exhibited variation according to weight status, television viewing habits, education level, and family size. The largest number of responses was coded to the category characterized by a negative attitude toward food advertising and a low locus of control. Parents in this category were more likely than others to be overweight/obese and heavy television viewers. Parents in the negative attitude to advertising and high locus of control category nominated a variety of parenting practices that could form the basis of parent education interventions. Conclusions: The results suggest that many Australian parents may feel disempowered in the face of high levels of advertising for unhealthy foods. The current voluntary regulatory code appears to be inadequate in scope and coverage to address this situation

Identifying the domains of context important to implementation science: a study protocol

Background There is growing recognition that “context” can and does modify the effects of implementation interventions aimed at increasing healthcare professionals’ use of research evidence in clinical practice. However, conceptual clarity about what exactly comprises “context” is lacking. The purpose of this research program is to develop, refine, and validate a framework that identifies the key domains of context (and their features) that can facilitate or hinder (1) healthcare professionals’ use of evidence in clinical practice and (2) the effectiveness of implementation interventions. Methods/design A multi-phased investigation of context using mixed methods will be conducted. The first phase is a concept analysis of context using the Walker and Avant method to distinguish between the defining and irrelevant attributes of context. This phase will result in a preliminary framework for context that identifies its important domains and their features according to the published literature. The second phase is a secondary analysis of qualitative data from 13 studies of interviews with 312 healthcare professionals on the perceived barriers and enablers to their application of research evidence in clinical practice. These data will be analyzed inductively using constant comparative analysis. For the third phase, we will conduct semi-structured interviews with key health system stakeholders and change agents to elicit their knowledge and beliefs about the contextual features that influence the effectiveness of implementation interventions and healthcare professionals’ use of evidence in clinical practice. Results from all three phases will be synthesized using a triangulation protocol to refine the context framework drawn from the concept analysis. The framework will then be assessed for content validity using an iterative Delphi approach with international experts (researchers and health system stakeholders/change agents). Discussion This research program will result in a framework that identifies the domains of context and their features that can facilitate or hinder: (1) healthcare professionals’ use of evidence in clinical practice and (2) the effectiveness of implementation interventions. The framework will increase the conceptual clarity of the term “context” for advancing implementation science, improving healthcare professionals’ use of evidence in clinical practice, and providing greater understanding of what interventions are likely to be effective in which contexts