Identifying co-regulating microrna groups

Background: Current miRNA target prediction tools have the common problem that their false positive rate is high. This renders identification of co-regulating groups of miRNAs and target genes unreliable. In this study, we describe a procedure to identify highly probable co-regulating miRNAs and the corresponding co-regulated gene groups. Our procedure involves a sequence of statistical tests: (1) identify genes that are highly probable miRNA targets; (2) determine for each such gene, the minimum number of miRNAs that co-regulate it with high probability; (3) find, for each such gene, the combination of the determined minimum size of miRNAs that co-regulate it with the lowest p-value; and (4) discover for each such combination of miRNAs, the group of genes that are co-regulated by these miRNAs with the lowest p-value computed based on GO term annotations of the genes.
Results: Our method identifies 4, 3 and 2-term miRNA groups that co-regulate gene groups of size at least 3 in human. Our result suggests some interesting hypothesis on the functional role of several miRNAs through a "guilt by association" reasoning. For example, miR-130, miR-19 and miR-101 are known neurodegenerative diseases associated miRNAs. Our 3-term miRNA table shows that miR-130/19/101 form a co-regulating group of rank 22 (p-value =1.16 × 10^-2). Since miR-144 is co-regulating with miR-130, miR-19 and miR-101 of rank 4 (p-value = 1.16 × 10^-2) in our 4-term miRNA table, this suggests hsa-miR-144 may be neurodegenerative diseases related miRNA. Conclusions: This work identifies highly probable co-regulating miRNAs, which are refined from the prediction by computational tools using (1) signal-to-noise ratio to get high accurate regulating miRNAs for every gene, and (2) Gene Ontology to obtain functional related co-regulating miRNA groups. Our result has partly been supported by biological experiments. Based on prediction by TargetScanS, we found highly probable target gene groups in the Supplementary Information. This result might help biologists to find small set of miRNAs for genes of interest rather than huge amount of miRNA set.

Democratizing health : consumer groups in the policy process

This timely book examines the role of consumer organisations in the health policy process. In an age of shifting boundaries between state and civil society, consumer groups are potentially drivers of democratisation in the health domain. Their activities bring new dynamics to relations between service providers, the medical profession, government agencies, and other policy actors. This book is unique in comprehensively exploring the opportunities and dilemmas of this type of activism, including sometimes ambiguous partnerships between consumer groups and stakeholders such as the pharmaceutical industry. These themes are explored within an internationally comparative frameThis book examines the important role of consumer activism within health policy in different national contexts. In an age of shifting boundaries between state and civil society, consumer groups are potentially drivers of democratization in the health domain. The expert contributors explore how their activities bring new dynamics to relations between service providers, the medical profession, government agencies, and other policy actors. This book is unique in comprehensively analysing the opportunities and dilemmas of this type of activism, including ambiguous partnerships between consumer groups and stakeholders such as the pharmaceutical industry. These themes are explored within an internationally comparative framework, with case studies from various countries. work, with case studies from many countries.

Introduction : consumer groups and the democratization of health policy

This book examines the important role of consumer activism within health policy in different national contexts. In an age of shifting boundaries between state and civil society, consumer groups are potentially drivers of democratization in the health domain. The expert contributors explore how their activities bring new dynamics to relations between service providers, the medical profession, government agencies, and other policy actors. This book is unique in comprehensively analysing the opportunities and dilemmas of this type of activism, including ambiguous partnerships between consumer groups and stakeholders such as the pharmaceutical industry. These themes are explored within an internationally comparative framework, with case studies from various countries. Students and researchers in the fields of health policy and sociology, public policy and social movements will find this relevant and path-breaking book enlightening. It will also prove invaluable for participants and activists in patient and health consumer organizations.

From activism to state inclusion : health consumer groups in Australia

This book examines the important role of consumer activism within health policy in different national contexts. In an age of shifting boundaries between state and civil society, consumer groups are potentially drivers of democratization in the health domain. The expert contributors explore how their activities bring new dynamics to relations between service providers, the medical profession, government agencies, and other policy actors. This book is unique in comprehensively analysing the opportunities and dilemmas of this type of activism, including ambiguous partnerships between consumer groups and stakeholders such as the pharmaceutical industry. These themes are explored within an internationally comparative framework, with case studies from various countries. Students and researchers in the fields of health policy and sociology, public policy and social movements will find this relevant and path-breaking book enlightening. It will also prove invaluable for participants and activists in patient and health consumer organizations.

MAAGs: the next generation. A study of the development of medical audit advisory groups and the arrangements for supporting clinical audit in primary care

Background: MAAGs have, historically, been disparate organisations with a lack of central direction, albeit with the same goal: to develop and support the performance of audit in primary care. This goal has been (and is being) achieved in a number of ways all over the country. In the last two years, MAAGs have witnessed many changes in primary care and are adapting themselves to suit these new arrangements at a local level.

Aim: To formalise our knowledge of where MAAGs are going, how they are getting there and the support they are receiving.

Method: A postal questionnaire to the 104 MAAGs in England and Wales, addressing 6 main issues of relevance to the development of MAAGs and the support they are receiving.

Results: At least two MAAGs have dissolved, leaving a possible total of 102 still in existence. Of these, 76 (74.5%) responded to the survey. The composition of the MAAG committee has changed dramatically since the inception of MAAGs in 1990, and staffing levels appear to have risen substantially. MAAGs appear to be more adequately funded by their health authorities than has previously been reported and many are actively seeking additional sources of funding. There is still large variation in levels of MAAG funding. Furthermore, funding is unrelated to the number of GPs or practices served. Security for MAAG staff appears to have been addressed in many areas, with 84% of MAAGs having at least one member of staff on a permanent employment contract. Many MAAGs are developing rolling programmes in an attempt to eliminate the short-sighted approach to the development of clinical audit that has existed since MAAGs were first set up.

Conclusion: Many MAAGs (with the obvious exception of those that have been dissolved) appear to be thriving without central direction or initiative. It is now evident that we were a little hasty in our concerns for the future of MAAGs beyond April 1996. It would seem that many organisations have taken the situation which arose two years ago as an opportunity to grow and develop in ways that may not have been possible within the confines of the Health Circular.

With guarded optimism? Evidence from focus groups of ‘mainstream’ Australians’ perceptions of Muslims

Studies of Australian perceptions of Muslims and Islam tend to be based on research into media representations of these themes. Additionally, most research on attitudes pertaining to social cohesion and security in the post-9/11 environment concentrates on the opinions of minority groups on these matters. The following study is drawn from materials extracted from focus group discussions relating to Islam, multiculturalism and security that took place with 119 Australians from so-called ethnic and religious majority groups (European descended, and identifying with Judaeo-Christian traditions or having no religious affiliation) in selected metropolitan and rural/regional centres of the state of Victoria in 2007–2008. This article is guided by the following research questions: How can ‘mainstream’ Australian attitudes towards Muslims be categorized? What concerns ‘mainstream’ Australians most about Muslims? Can these attitudes be considered to be Islamophobic? If not, how else may we classify these attitudes? Although some participants voiced very strong, critical and at times unflattering and potentially antagonistic opinions of Muslims, most contributors were guardedly optimistic that current tensions with and controversies surrounding Australia’s Muslims would subside, and that Muslims would soon become well established within Australian society, as previous generations of migrants have since World War II.

Dorsal and ventral medullary catecholamine cell groups contribute differentially to systemic interleukin-1beta-induced hypothalamic pituitary adrenal axis responses

Medial parvocellular paraventricular corticotropin-releasing hormone (mPVN CRH) cells are critical in generating hypothalamic-pituitary-adrenal (HPA) axis responses to systemic interleukin-1beta (IL-1beta). However, although it is understood that catecholamine inputs are important in initiating mPVN CRH cell responses to IL-1beta, the contributions of distinct brainstem catecholamine cell groups are not known. We examined the role of nucleus tractus solitarius (NTS) and ventrolateral medulla (VLM) catecholamine cells in the activation of mPVN CRH, hypothalamic oxytocin (OT) and central amygdala cells in response to IL-1beta (1 microg/kg, i.a.). Immunolabelling for the expression of c-fos was used as a marker of neuronal activation in combination with appropriate cytoplasmic phenotypic markers. First we confirmed that PVN 6-hydroxydopamine lesions, which selectively depleted catecholaminergic terminals, significantly reduced IL-1beta-induced mPVN CRH cell activation. The contribution of VLM (A1/C1 cells) versus NTS (A2 cells) catecholamine cells to mPVN CRH cell responses was then examined by placing ibotenic acid lesions in either the VLM or NTS. The precise positioning of these lesions was guided by prior retrograde tracing studies in which we mapped the location of IL-1beta-activated VLM and NTS cells that project to the mPVN. Both VLM and NTS lesions reduced the mPVN CRH and OT cell responses to IL-1beta. Unlike VLM lesions, NTS lesions also suppressed the recruitment of central amygdala neurons. These studies provide novel evidence that both the NTS and VLM catecholamine cells have important, but differential, contributions to the generation of IL-1beta-induced HPA axis responses.

Stressor categorization : acute physical and psychological stressors elicit distinctive recruitment patterns in the amygdala and in medullary noradrenergic cell groups

It has been hypothesized that the brain categorizes stressors and utilizes neural response pathways that vary in accordance with the assigned category. If this is true, stressors should elicit patterns of neuronal activation within the brain that are category-specific. Data from previous immediate–early gene expression mapping studies have hinted that this is the case, but interstudy differences in methodology render conclusions tenuous. In the present study, immunolabelling for the expression of c-fos was used as a marker of neuronal activity elicited in the rat brain by haemorrhage, immune challenge, noise, restraint and forced swim. All stressors elicited c-fos expression in 25–30% of hypothalamic paraventricular nucleus corticotrophin-releasing-factor cells, suggesting that these stimuli were of comparable strength, at least with regard to their ability to activate the hypothalamic–pituitary–adrenal axis. In the amygdala, haemorrhage and immune challenge both elicited c-fos expression in a large number of neurons in the central nucleus of the amygdala, whereas noise, restraint and forced swim primarily elicited recruitment of cells within the medial nucleus of the amygdala. In the medulla, all stressors recruited similar numbers of noradrenergic (A1 and A2) and adrenergic (C1 and C2) cells. However, haemorrhage and immune challenge elicited c-fos expression in subpopulations of A1 and A2 noradrenergic cells that were significantly more rostral than those recruited by noise, restraint or forced swim. The present data support the suggestion that the brain recognizes at least two major categories of stressor, which we have referred to as ‘physical’ and ‘psychological’. Moreover, the present data suggest that the neural activation footprint that is left in the brain by stressors can be used to determine the category to which they have been assigned by the brain.

Anaphors in casual and controlled talks groups of Iranian EFL learners

By relying mainly on the accessibility approach to anaphora, this article intends to analyze the types, distributions and retrieval of anaphors in two forms of spoken discourse: casual and controlled talk. For the specific purposes of the study, twenty sophomore Iranian students were randomly selected to conduct the talks. The subjects were divided into two groups of casual and controlled talk. According to the settings and adopted topics, the overall casual talk group was further divided into two groups of dorm and academic talk. In the end, it was observed that as the talk situations vary, types, frequencies, distances, retrieval qualities and thematic structure (patterning) of anaphors undergo dramatic changes too. Further analyses of the obtained data show that the number of pronominal anaphors is by far more than NP anaphors in dorm casual talk whereas in academic casual talk the number of NP anaphors exceeds that of the former talk groups. However, the distribution of anaphors in the performance of controlled talk groups has shown to be more moderate with regard to the types of anaphors used in it. Overall, the distributional patterns of various anaphoric devices in different talk situations are considered to be a function of the speakers’ evaluation of the cognitive states of the listeners/addressees.
Average distances and frequencies of the different types of zero, pronominal, and NP anaphors have also been shown to undergo dramatic changes as talk situations vary.

Health system costs of diseases and injury in Australia 1993-94 : an analysis of costs, service use and mortality for major disease and injury groups

Provides a systematic analysis of the health system use and costs associated with specific disease and injury groups in Australia in 1993-94. The estimates are presented in a consistent format and are derived using a methodology that ensures the results add across disease, age and sex groups to total Australian health expenditures for 1993-94.

The L(2,1)-labelling problem for cubic Cayley graphs on dihedral groups

A k-L(2,1)-labelling of a graph G is a mapping f:V(G)→{0,1,2,…,k} such that |f(u)−f(v)|≥2 if uv∈E(G) and f(u)≠f(v) if u,v are distance two apart. The smallest positive integer k such that G admits a k-L(2,1)-labelling is called the λ-number of G. In this paper we study this quantity for cubic Cayley graphs (other than the prism graphs) on dihedral groups, which are called brick product graphs or honeycomb toroidal graphs. We prove that the λ-number of such a graph is between 5 and 7, and moreover we give a characterisation of such graphs with λ-number 5.