Harmonization of trade in services by APEC members

This study maps out the degree of services trade liberalization by the APEC members toward achieving a Free Trade Area of the Asia-Pacific (FTAAP) and makes some comparative analyses. The study finds that the commitment level differs greatly between sensitive and less sensitive sectors, and that the commitment level under the ASEAN Framework Agreement (AFAS) package 8 is the highest among the four FTAs studied. It also finds that there are cross-country and sector-wide similarities in the pattern of service sector commitment under and across each of the FTAs; this implies that the shared domestic sensitivities can be overcome by an APEC-wide economic cooperation scheme for enhancing competitiveness (through, e.g., the Trans-Pacific Strategic Economic Partnership Agreement or TPP).

Ukraine, Russia and the need for more flexibility in EU foreign policy-making. CEPS Policy Brief No. 320, 25 July 2014

After the illegal annexation of Crimea and Russia’s indirect responsibility for the downing of Malaysia Airlines flight MH17 in eastern Ukraine, Steven Blockmans asks what it will take before the EU is able to confront a conflict on its borders and prove to both its own citizens and third countries that it has a meaningful role to play in foreign policy. With numerous competing national interests and some member states unwilling to pay different prices for collective action, any sector-wide EU sanctions are likely to lack serious bite. In an effort to paper over the cracks, the author makes a number of recommendations for policy-makers.

Overexpression of sonic hedgehog suppresses embryonic hair follicle morphogenesis

The Sonic Hedgehog (Shh) signalling pathway plays a central role in the development of the skin and hair follicle and is a major determinant of skin tumorigenesis, most notably of basal cell carcinoma (BCC). Various mouse models involving either ablation or overexpression of key members of the Shh signalling pathway display a range of skin tumours. To further examine the role of Shh in skin development. we have overexpressed Shh in a subset of interfollicular basal cells from 12.5 dpc under the control of the human keratin 1 (HK1) promoter. The HK1-Shh transgenic mice display a range of skin anomalies, including highly pigmented inguinal lesions and regions of alopecia. The most striking hair follicle phenotype is a suppression in embryonic follicle development between 14.0 and 19.0 dpc, resulting in a complete absence of guard, awl, and auchene hair fibres. These data indicate that alternative signals are responsible for the development of different hair follicles and point to a major role of Shh signalling in the morphogenesis of guard, awl, and auchene hair fibres. Through a comparison with other mouse models, the characteristics of the HK1-Shh transgenic mice suggest that the precise timing and site of Shh expression are key in dictating the resultant skin and tumour phenotype. 2003 Elsevier Inc. All rights reserved.

5 '-Untranslated regions with multiple upstream AUG codons can support low-level translation via leaky scanning and reinitiation

Upstream AUGs (uAUGs) and upstream open reading frames (uORFs) are common features of mRNAs that encode regulatory proteins and have been shown to profoundly influence translation of the main ORF. In this study, we employed a series of artificial 5'-untranslated regions (5'-UTRs) containing one or more uAUGs/uORFs to systematically assess translation initiation at the main AUG by leaky scanning and reinitiation mechanisms. Constructs containing either one or two uAUGs in varying contexts but without an in-frame stop codon upstream of the main AUG were used to analyse the leaky scanning mechanism. This analysis largely confirmed the ranking of different AUG contextual sequences that was determined previously by Kozak. In addition, this ranking was the same for both the first and second uAUGs, although the magnitude of initiation efficiency differed. Moreover, similar to10% of ribosomes exhibited leaky scanning at uAUGs in the most favourable context and initiated at a downstream AUG. A second group of constructs containing different numbers of uORFs, each with optimal uAUGs, were used to measure the capacity for reinitiation. We found significant levels of initiation at the main ORF even in constructs containing four uORFs, with nearly 10% of ribosomes capable of reinitiating five times. This study shows that for mRNAs containing multiple uORFs/uAUGs, ribosome reinitiation and leaky scanning are efficient mechanisms for initiation at their main AUGs.

Evolutionary conservation and murine embryonic expression of the gene encoding the SERTA domain-containing protein CDCA4 (HEPP)

Cdca4 (Hepp) was originally identified as a gene expressed specifically in hematopoietic progenitor cells as opposed to hematopoietic stem cells. More recently, it has been shown to stimulate p53 activity and also lead to p53-independent growth inhibition when overexpressed. We independently isolated the murine Cdca4 gene in a genomic expression-based screen for genes involved in mammalian craniofacial development, and show that Cdca4 is expressed in a spatio-temporally restricted pattern during mouse embryogenesis. In addition to expression in the facial primordia including the pharyngeal arches, Cdca4 is expressed in the developing limb buds, brain, spinal cord, dorsal root ganglia, teeth, eye and hair follicles. Along with a small number of proteins from a range of species, the predicted CDCA4 protein contains a novel SERTA motif in addition to cyclin A-binding and PHD bromodomain-binding regions of homology. While the function of the SERTA domain is unknown, proteins containing this domain have previously been linked to cell cycle progression and chromatin remodelling. Using in silico database mining we have extended the number of evolutionarily conserved orthologues of known SERTA domain proteins and identified an uncharacterised member of the SERTA domain family, SERTAD4, with orthologues to date in human, mouse, rat, dog, cow, Tetraodon and chicken. Immunolocalisation of transiently and stably transfected epitope-tagged CDCA4 protein in mammalian cells suggests that it resides predominantly in the nucleus throughout all stages of the cell cycle. (c) 2006 Elsevier B.V. All rights reserved.

Quantitative analysis of MC1R gene expression in human skin cell cultures

To address the issue of melanocortin-1 receptor (MC1R) expression in non-melanocytic cells, we have quantitatively evaluated the relative expression levels of both MC1R mRNA and protein in a subset of different cell types. Using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) at high cycle numbers, we detected MC1R mRNA in all cell types examined, including human embryonic kidney-293 (HEK 293) cells, a cell type widely used as a negative control in melanocortin expression studies. Quantitative real-time PCR revealed the highest levels of MC1R transcripts were in melanocytic cells, whereas the keratinocyte and fibroblast cell cultures examined had only a low level of expression, similar to that of HEK 293 cells. Antibody mediated detection of MC1R protein in membrane extracts demonstrated exogenous receptor in MC1R transfected cell lines, as well as endogenous MC1R in melanoma cells. However, radioligand binding procedures were required to detect MC1R protein of normal human melanocytes and no surface expression of MC1R was detected in any of the non-melanocytic cells examined. This was consistent with their low level of mRNA, and suggests that, if present, the levels of surface receptor are significantly lower than that in melanocytes. The capacity of such limited levels of MC1R protein to influence non-melanocytic skin cell biology would likely be severely compromised. Indeed, the MC1R agonist [NIe(4), D-Phe(7)] alpha-melanocyte stimulating hormone (NDP-MSH) was unable to elevate intracellular cyclic adenosine monophosphate (cAMP) levels in the keratinocyte and fibroblast cells examined, whereas a robust increase was elicited in melanocytes. Although there are a variety of cell types with detectable MC1R mRNA, the expression of physiologically significant levels of the receptor may be more restricted than the current literature indicates, and within epidermal tissue may be limited to the melanocyte

Transcriptional network dynamics in macrophage activation

Transcriptional regulatory networks govern cell differentiation and the cellular response to external stimuli. However, mammalian model systems have not yet been accessible for network analysis. Here, we present a genome-wide network analysis of the transcriptional regulation underlying the mouse macrophage response to bacterial lipopolysaccharide (LPS). Key to uncovering the network structure is our combination of time-series cap analysis of gene expression with in silico prediction of transcription factor binding sites. By integrating microarray and qPCR time-series expression data with a promoter analysis, we find dynamic subnetworks that describe how signaling pathways change dynamically during the progress of the macrophage LPS response, thus defining regulatory modules characteristic of the inflammatory response. In particular, our integrative analysis enabled us to suggest novel roles for the transcription factors ATF-3 and NRF-2 during the inflammatory response. We believe that our system approach presented here is applicable to understanding cellular differentiation in higher eukaryotes. (c) 2006 Elsevier Inc. All rights reserved.

Comparative cost-effectiveness of policy instruments for reducing the global burden of alcohol, tobacco and illicit drug use

Alcohol, tobacco and illicit drug use together pose a formidable challenge to international public health. Building on earlier estimates of the demonstrated burden of alcohol, tobacco and illicit drug use at the global level, this review aims to consider the comparative cost-effectiveness of evidence-based interventions for reducing the global burden of disease from these three risk factors. Although the number of published cost-effectiveness studies in the addictions field is now extensive ( reviewed briefly here) there are a series of practical problems in using them for sector-wide decision making, including methodological heterogeneity, differences in analytical reference point and the specificity of findings to a particular context. In response to these limitations, a more generalised form of cost-effectiveness analysis (CEA) is proposed, which enables like-with-like comparisons of the relative efficiency of preventive or individual-based strategies to be made, not only within but also across diseases or their risk factors. The application of generalised CEA to a range of personal and non-personal interventions for reducing the burden of addictive substances is described. While such a development avoids many of the obstacles that have plagued earlier attempts and in so doing opens up new opportunities to address important policy questions, there remain a number of caveats to population-level analysis of this kind, particularly when conducted at the global level. These issues are the subject of the final section of this review.

Genes and gene expression in human alcoholic brain

Chronic alcoholism leads to localized brain damage, which is prominent in superior frontal cortex but mild in motor cortex. The likelihood of developing alcohol dependence is associated with genetic markers. GABA-A receptor expression differs between alcoholics and controls, whereas glutamate receptor differences are muted. We determined whether genotype differentiated the localized expression of glutamate N-methyl-D-aspartate (NMDA) and GABA-A receptors to influence the severity of alcohol-induced brain damage. Cerebral cortex tissue was obtained at autopsy from alcoholics without disease comorbid with alcoholics, alcoholics with cirrhosis, and matched controls. DRD2A, DRD2B, GABRB2, SLC1A2, and 5HTT genotypes did not divide alcoholic cases and controls on NMDA receptor parameters. In contrast, a specific alcohol dehydrogenase (ADHIC) genotype interacted significantly with NMDA efficacy and affinity in a region-specific manner SLC1A2 (glutamate transporter-2) genotype interacted significantly with local GABAA receptor b subunit mRNA expression, and ADHIC, DRD2B, SLC1A2, and APOE genotypes with b subunit isoform protein expression. In the latter instance, possession of the alcoholism- associated allele altered b isoform protein expression patterns toward a less-efficacious form of the GABA-A receptor in the pathologically vulnerable region. GABRB2 and GRIN2B (NMDA receptor 2B subunit} Genotypes were associated with significant regional difference in the pattern of b subunit protein isoform expression, but this was not influenced by alcoholism status. Genotype may modulate amino acid transmission locally so as to mediate neuronal vulnerability. This has implications for the effectiveness of pharmacological interventions aimed at ameliorating brain damage and, possibly, dependence.

Inventory management for the health sector: ABC analysis approach

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Environmental Tax on Products and Services Based on Their Carbon Footprint: A Case Study of the Pulp and Paper Sector

The main aim of this work is to define an environmental tax on products and services based on their carbon footprint. We examine the relevance of conventional life cycle analysis (LCA) and environmentally extended input-output analysis (EIO) as methodological tools to identify emission intensities of products and services on which the tax is based. The short-term price effects of the tax and the policy implications of considering non-GHG are also analyzed. The results from the specific case study on pulp production show that the environmental tax rate based on the LCA approach (1,8%) is higher than both EIO approaches (0,8% for product and 1,4% for industry approach), but they are comparable. Even though LCA is more product specific and provides detailed analysis, EIO would be the more relevant approach to apply economy wide environmental tax. When the environmental tax considers non-GHG emissions instead of only CO2, sectors such as agriculture, mining of coal and extraction of peat, and food exhibit higher environmental tax and price effects. Therefore, it is worthwhile for policy makers to pay attention on the implication of considering only CO2 tax or GHG emissions tax in order for such a policy measure to be effective and meaningful. Keywords: Environmental tax; Life cycle analysis; Environmental input-output analysis.

Speech by Mr. Micheál Martin TD – Meeting The Challenges Of Cultural Diversity In The Irish Healthcare Sector

It gives me great pleasure to accept the invitation to address this conference on “Meeting the Challenges of Cultural Diversity in the Irish Healthcare Sector” which is being organised by the Irish Health Services Management Institute in partnership with the National Consultative Committee on Racism and Interculturalism. The conference provides an important opportunity to develop our knowledge and understanding of the issues surrounding cultural diversity in the health sector from the twin perspectives of patients and staff. Cultural diversity has over recent years become an increasingly visible aspect of Irish society bringing with it both opportunities and challenges. It holds out great possibilities for the enrichment of all who live in Ireland but it also challenges us to adapt creatively to the changes required to realise this potential and to ensure that the experience is a positive one for all concerned but particularly for those in the minority ethnic groups. In the last number of years in particular, the focus has tended to be on people coming to this country either as refugees, asylum seekers or economic migrants. Government figures estimate that as many as 340,000 immigrants are expected in the next six years. However ethnic and cultural diversity are not new phenomena in Ireland. Travellers have a long history as an indigenous minority group in Ireland with a strong culture and identity of their own. The changing experience and dynamics of their relationship with the wider society and its institutions over time can, I think, provide some valuable lessons for us as we seek to address the more numerous and complex issues of cultural diversity which have arisen for us in the last decade. Turning more specifically to the health sector which is the focus of this conference, culture and identity have particular relevance to health service policy and provision in that The first requirement is that we in the health service acknowledge cultural diversity and the differences in behaviours and in the less obvious areas of values and beliefs that this often implies. Only by acknowledging these differences in a respectful way and informing ourselves of them can we address them. Our equality legislation – The Employment Equality Act, 1998 and the Equal Status Act, 2000 – prohibits discrimination on nine grounds including race and membership of the Traveller community. The Equal Status Act prohibits discrimination on an individual basis in relation to the nine grounds while for groups it provides for the promotion of equality of opportunity. The Act applies to the provision of services including health services. I will speak first about cultural diversity in relation to the patient. In this respect it is worth mentioning that the recognition of cultural diversity and appropriate responses to it were issues which were strongly emphasised in the public consultation process which we held earlier this year in the context of developing National Anti-Poverty targets for the health sector and also our new national health strategy. Awareness and sensitivity training for staff is a key requirement for adapting to a culturally diverse patient population. The focus of this training should be the development of the knowledge and skills to provide services sensitive to cultural diversity. Such training can often be most effectively delivered in partnership with members of the minority groups themselves. I am aware that the Traveller community, for example, is involved in in-service training for health care workers. I am also aware that the National Consultative Committee on Racism and Interculturalism has been involved in training with the Eastern Regional Health Authority. We need to have more such initiatives. A step beyond the sensitivity training for existing staff is the training of members of the minority communities themselves as workers in our health services. Again the Traveller community has set an example in this area with its Primary Health Care Project for Travellers. The Primary Health Care for Travellers Project was established in 1994 as a joint partnership initiative with the Eastern Health Board and Pavee Point, with ongoing technical assistance being provided from the Department of Community Health and General Practice, Trinity College, Dublin. This project was the first of its kind in the country and has facilitated The project included a training course which concentrated on skills development, capacity building and the empowerment of Travellers. This confidence and skill allowed the Community Health Workers to go out and conduct a baseline survey to identify and articulate Travellers’ health needs. This was the first time that Travellers were involved in this process; in the past their needs were assumed. The results of the survey were fed back to the community and they prioritised their needs and suggested changes to the health services which would facilitate their access and utilisation. Ongoing monitoring and data collection demonstrates a big improvement in levels of satisfaction and uptake and ulitisation of health services by Travellers in the pilot area. This Primary Health Care for Travellers initiative is being replicated in three other areas around the country and funding has been approved for a further 9 new projects. This pilot project was the recipient of a WHO 50th anniversary commemorative award in 1998. The project is developing as a model of good practice which could inspire further initiatives of this type for other minority groups. Access to information has been identified in numerous consultative processes as a key factor in enabling people to take a proactive approach to managing their own health and that of their families and in facilitating their access to health services. Honouring our commitment to equity in these areas requires that information is provided in culturally appropriate formats. The National Health Promotion Strategy 2000-2005, for example, recognises that there exists within our society many groups with different requirements which need to be identified and accommodated when planning and implementing health promotion interventions. These groups include Travellers, refugees and asylum seekers, people with intellectual, physical or sensory disability and the gay and lesbian community. The Strategy acknowledges the challenge involved in being sensitive to the potential differences in patterns of poor health among these different groups. The Strategic aim is to promote the physical, mental and social well-being of individuals from these groups. The objective of the Strategy on these issues are: While our long term aim may be to mainstream responses so that our health services is truly multicultural, we must recognise the need at this point in time for very specific focused responses particularly for groups with poor health status such as Travellers and also for refugees and asylum seekers. In the case of refugees and asylum seekers examples of targeted services are screening for communicable diseases – offered on a voluntary basis – and psychological support services for those who have suffered trauma before coming here. The two approaches of targeting and mainstreaming are not mutually exclusive. A combination of both is required at this point in time but the balance between them must be kept under constant review in the light of changing needs. A major requirement if we are to meet the challenge of cultural diversity is an appropriate data and research base. I think it is important that we build up our information and research data base in partnership with the minority groups themselves. We must establish what the health needs of diverse groups are; we must monitor uptake of services and how well we are responding to needs and we must monitor outcomes and health status. We must also examine the impact of the policies in other sectors on the health of minority groups. The National Health Information Strategy, currently being developed, and the recently published National Strategy for Health Research – Making Knowledge Work for Health provide important frameworks within which we can improve our data and research base. A culturally diverse health sector workforce – challenges and opportunities The Irish health service can benefit greatly from successful international recruitment. There has been a strong non-national representation amongst the medical profession for more than 30 years. More recently there have been significant increases in other categories of health service workers from overseas. The Department recognises the enormous value that overseas recruitment brings over a wide range of services and supports the development of effective and appropriate recruitment strategies in partnership with health service employers. These changes have made cultural diversity an important issue for all health service organisations. Diversity in the workplace is primarily about creating a culture that seeks, respects, values and harnesses difference. This includes all the differences that when added together make each person unique. So instead of the focus being on particular groups, diversity is about all of us. Change is not about helping “them” to join “us” but about critically looking at “us” and rooting out all aspects of our culture that inappropriately exclude people and prevent us from being inclusive in the way we relate to employees, potential employees and clients of the health service. International recruitment benefits consumers, Irish employees and the overseas personnel alike. Regardless of whether they are employed by the health service, members of minority groups will be clients of our service and consequently we need to be flexible in order to accommodate different cultural needs. For staff, we recognise that coming from other cultures can be a difficult transition. Consequently health service employers have made strong efforts to assist them during this period. Many organisations provide induction courses, religious facilities (such as prayer rooms) and help in finding suitable accommodation. The Health Service Employers Agency (HSEA) is developing an equal opportunities/diversity strategy and action plans as well as training programmes to support their implementation, to ensure that all health service employment policies and practices promote the equality/diversity agenda to continue the development of a culturally diverse health service. The management of this new environment is extremely important for the health service as it offers an opportunity to go beyond set legal requirements and to strive for an acceptance and nurturing of cultural differences. Workforce cultural diversity affords us the opportunity to learn from the working practices and perspectives of others by allowing personnel to present their ideas and experience through teamwork, partnership structures and other appropriate fora, leading to further improvement in the services we provide. It is important to ensure that both personnel units and line managers communicate directly with their staff and demonstrate by their actions that they intend to create an inclusive work place which doesn´t demand that minority staff fit. Contented, valued employees who feel that there is a place for them in the organisation will deliver a high quality health service. Your conference here today has two laudable aims – to heighten awareness and assist health care staff to work effectively with their colleagues from different cultural backgrounds and to gain a greater understanding of the diverse needs of patients from minority ethnic backgrounds. There is a synergy in these aims and in the tasks to which they give rise in the management of our health service. The creative adaptations required for one have the potential to feed into the other. I would like to commend both organisations which are hosting this conference for their initiative in making this event happen, particularly at this time – Racism in the Workplace Week. I look forward very much to hearing the outcome of your deliberations. Thank you.

Molecular genetics of rare hereditary diseases via genome-wide and integrated approaches

ABSTRACTThe Online Mendelian Inheritance in Man database (OMIM) reports about 3000 Mendelian diseases of known causal gene and about 2000 that remain to be mapped. These cases are often difficult to solve because of the rareness of the disease, the structure of the family (too big or too small) or the heterogeneity of the phenotype. The goal of this thesis is to explore the current genetic tools, before the advent of ultra high throughput sequencing, and integrate them in the attempt to map the genes behind the four studied cases. In this framework we have studied a small family with a recessive disease, a modifier gene for the penetrance of a dominant mutation, a large extended family with a cardiac phenotype and clinical and/or allelic heterogeneity and we have molecularly analyzed a balanced chromosomal translocation.RESUMELa base de données des maladies à transmission mendélienne, Online Mendelian Inheritance in Man (OMIM), contient environ 3000 affections à caractère mendélien pour lesquelles le gène responsable est connu et environ 2000 qui restent à élucider.Les cas restant à résoudre sont souvent difficiles soit par le caractère intrinsèquement rare de ces maladies soit à cause de difficultés structurelles (famille trop petite ou trop étendue) ou hétérogénéité du phénotype ou génétique. Cette thèse s'inscrit avant l'arrivée des nouveaux outils de séquençage à haut débit. Son but est d'explorer les outils génétiques actuels, et de les intégrer pour trouver les gènes impliqués dans quatre cas représentant chacun une situation génétique différente : nous avons étudié une famille de quatre individus avec une transmission récessive, recherché un gène modificateur de la pénétrance de mutations dominantes, étudié une famille étendue présentant un phénotype cardiaque cliniquement et/ou allèliquement hétérogène et nous avons fait l'analyse moléculaire d'une translocation chromosomique balancée.

Future trends of the World Wide Web in the food and beverage sector in Spain

Extended abstract.