Proteomic characterization of the multiple forms of the PLAs from the venom of the social wasp Polybia paulista

The phospholipases A(1) (PLA(1)s) from the venom of the social wasp Polybia paulista occur as a mixture of different molecular forms. To characterize the molecular origin of these structural differences, an experimental strategy was planned combining the isolation of the pool of PLAs from the wasp venom with proteomic approaches by using 2-D, MALDI-TOF-TOF MS and classical protocols of protein chemistry, which included N- and C-terminal sequencing. The existence of an intact form of PLA(1) and seven truncated forms was identified, apparently originating from controlled proteolysis of the intact protein; in addition to this, four of these truncated forms also presented carbohydrates attached to their molecules. Some of these forms are immunoreactive to specific-IgE, while others are not. These observations permit to raise the hypothesis that naturally occurring proteolysis of PLA(1), combined with protein glycosylation may create a series of different molecular forms of these proteins, with different levels of allergenicity. Two forms of PLA(2)s, apparently related to each other, were also identified; however, it was not possible to determine the molecular origin of the differences between both forms, except that one of them was glycosylated. None of these forms were immunoreactive to human specific IgE.

Validation of the spanish version of the multiple sclerosis international quality of life (musiqol) questionnaire

BACKGROUND: The Multiple Sclerosis International Quality Of Life (MusiQoL) questionnaire, a 31-item, multidimensional, self-administrated questionnaire that is available in 14 languages including Spanish, has been validated using a large international sample. We investigated the validity and reliability of the Spanish version of MusiQoL in Spain. METHODS: Consecutive patients with different types and severities of multiple sclerosis (MS) were recruited from 22 centres across Spain. All patients completed the MusiQoL questionnaire, the 36-Item Short Form (SF-36) health survey, and a symptoms checklist at baseline and 21 days later. External validity, internal consistency, reliability and reproducibility were tested. RESULTS: A total of 224 Spanish patients were evaluated. Dimensions of MusiQoL generally demonstrated a high internal consistency (Cronbach's alpha: 0.70-0.92 for all but two MusiQoL domain scores). External validity testing revealed that the MusiQoL index score correlated significantly with all SF-36 dimension scores (Pearson's correlation: 0.46-0.76), reproducibility was satisfactory (intraclass correlation coefficient: 0.60-0.91), acceptability was high, and the time taken to complete the 31-item questionnaire was reasonable (mean [standard deviation]: 9.8 [11.8] minutes). CONCLUSIONS: The Spanish version of the MusiQoL questionnaire appears to be a valid and reliable instrument for measuring quality of life in patients with MS in Spain and constitutes a useful instrument to measure health-related quality of life in the clinical setting.

Fine mapping and functional analysis of the multiple sclerosis risk gene CD6.

CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2(nd) SRCR domain with susceptibility to MS (P max(T) permutation = 1×10(-4)). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. - CD4(+) naïve cells, P = 0.0001; CD8(+) naïve cells, P<0.0001; CD4(+) and CD8(+) central memory cells, P = 0.01 and 0.05, respectively; and natural killer T (NKT) cells, P = 0.02; with the protective haplotype (RA) showing higher expression of CD6. However, no significant changes were observed in natural killer (NK) cells, effector memory and terminally differentiated effector memory T cells. Our findings reveal that this new MS-associated CD6 risk haplotype significantly modifies expression of CD6 on CD4(+) and CD8(+) T cells.

Responsiveness of the Multiple Sclerosis International Quality of Life questionnaire to disability change: a longitudinal study.

BACKGROUND Responsiveness, defined as the ability to detect a meaningful change, is a core psychometric property of an instrument measuring quality of life (QoL) rarely reported in multiple sclerosis (MS) studies. OBJECTIVE To assess the responsiveness of the Multiple Sclerosis International Quality of Life (MusiQoL) questionnaire to change in disability over 24 months, defined by change in the Expanded Disability Status Scale (EDSS) score. METHODS Patients with MS were enrolled into a multicenter, longitudinal observational study. QoL was assessed using both the MusiQoL and the 36-Item Short-Form (SF-36) instruments at baseline and every 6 months thereafter up to month 24; neurological assessments, including EDSS score, were performed at each evaluation. RESULTS The 24-month EDSS was available for 524 patients. In the 107 worsened patients, two specific dimensions of MusiQoL, the sentimental and sexual life and the relationships with health care system dimensions, and 'physical' scores of SF-36 showed responsiveness. CONCLUSIONS Whereas specific dimensions of MusiQoL identified EDSS changes, the MusiQoL index did not detect disability changes in worsened MS patients in a 24-month observational study. Future responsiveness validation studies should include longer follow-up and more representative samples.

Operational benefits and challenges of the use of fingerprint statistical models: a field study

Research projects aimed at proposing fingerprint statistical models based on the likelihood ratio framework have shown that low quality finger impressions left on crime scenes may have significant evidential value. These impressions are currently either not recovered, considered to be of no value when first analyzed by fingerprint examiners, or lead to inconclusive results when compared to control prints. There are growing concerns within the fingerprint community that recovering and examining these low quality impressions will result in a significant increase of the workload of fingerprint units and ultimately of the number of backlogged cases. This study was designed to measure the number of impressions currently not recovered or not considered for examination, and to assess the usefulness of these impressions in terms of the number of additional detections that would result from their examination.

Optogenetic Interrogation of Dopaminergic Modulation of the Multiple Phases of Reward-Seeking Behavior.

Phasic activation of dopaminergic neurons is associated with reward-predicting cues and supports learning during behavioral adaptation. While noncontingent activation of dopaminergic neurons in the ventral tegmental are (VTA) is sufficient for passive behavioral conditioning, it remains unknown whether the phasic dopaminergic signal is truly reinforcing. In this study, we first targeted the expression of channelrhodopsin-2 to dopaminergic neurons of the VTA and optimized optogenetically evoked dopamine transients. Second, we showed that phasic activation of dopaminergic neurons in freely moving mice causally enhances positive reinforcing actions in a food-seeking operant task. Interestingly, such effect was not found in the absence of food reward. We further found that phasic activation of dopaminergic neurons is sufficient to reactivate previously extinguished food-seeking behavior in the absence of external cues. This was also confirmed using a single-session reversal paradigm. Collectively, these data suggest that activation of dopaminergic neurons facilitates the development of positive reinforcement during reward-seeking and behavioral flexibility.

Simulated Patient as Co-facilitators: Benefits and Challenges of the Interprofessional Team OSCE (Submission #9350).

Hypothesis: The quality of care for chronic patients depends on the collaborative skills of the healthcare providers.1,2 The literature lacks reports of the use of simulation to teach collaborative skills in non-acute care settings. We posit that simulation offers benefits for supporting the development of collaborative practice in non-acute settings. We explored the benefits and challenges of using an Interprofessional Team - Objective Structured Clinical Examination (IT-OSCE) as a formative assessment tool. IT-OSCE is an intervention which involves an interprofessional team of trainees interacting with a simulated patient (SP) enabling them to practice collaborative skills in non-acute care settings.5 A simulated patient are people trained to portray patients in a simulated scenario for educational purposes.6,7 Since interprofessional education (IPE) ultimately aims to provide collaborative patient-centered care.8,9 We sought to promote patient-centeredness in the learning process. Methods: The IT-OSCE was conducted with four trios of students from different professions. The debriefing was co-facilitated by the SP with a faculty. The participants were final-year students in nursing, physiotherapy and medicine. Our research question focused on the introduction of co-facilitated (SP and faculty) debriefing after an IT-OSCE: 1) What are the benefits and challenges of involving the SP during the debriefing? and 2) To evaluate the IT-OSCE, an exploratory case study was used to provide fine grained data 10, 11. Three focus groups were conducted - two with students (n=6; n=5), one with SPs (n=3) and one with faculty (n=4). Audiotapes were transcribed for thematic analysis performed by three researchers, who found a consensus on the final set of themes. Results: The thematic analysis showed little differentiation between SPs, student and faculty perspectives. The analysis of transcripts revealed more particularly, that the SP's co-facilitation during the debriefing of an IT-OSCE proved to be feasible. It was appreciated by all the participants and appeared to value and to promote patient-centeredness in the learning process. The main challenge consisted in SPs feedback, more particularly in how they could report accurate observations to a students' group rather than individual students. Conclusion: In conclusion, SP methodology using an IT-OSCE seems to be a useful and promising way to train collaborative skills, aligning IPE, simulation-based team training in a non-acute care setting and patient-centeredness. We acknowledge the limitations of the study, especially the small sample and consider the exploration of SP-based IPE in non-acute care settings as strength. Future studies could consider the preparation of SPs and faculty as co-facilitators. References: 1. Borrill CS, Carletta J, Carter AJ, et al. The effectiveness of health care teams in the National Health Service. Aston centre for Health Service Organisational Research. 2001. 2. Reeves S, Lewin S, Espin S, Zwarenstein M. Interprofessional teamwork for health and social care. Oxford: Wiley-Blackwell; 2010. 3. Issenberg S, McGaghie WC, Petrusa ER, Gordon DL, Scalese RJ. Features and uses of high-fidelity medical simulations that lead to effective learning - a BEME systematic review. Medical Teacher. 2005;27(1):10-28. 4. McGaghie W, Petrusa ER, Gordon DL, Scalese RJ. A critical review of simulation-based medical education research: 2003-2009. Medical Education. 2010;44(1):50-63. 5. Simmons B, Egan-Lee E, Wagner SJ, Esdaile M, Baker L, Reeves S. Assessment of interprofessional learning: the design of an interprofessional objective structured clinical examination (iOSCE) approach. Journal of Interprofessional Care. 2011;25(1):73-74. 6. Nestel D, Layat Burn C, Pritchard SA, Glastonbury R, Tabak D. The use of simulated patients in medical education: Guide Supplement 42.1 - Viewpoint. Medical teacher. 2011;33(12):1027-1029. Disclosures: None (C) 2014 by Lippincott Williams & Wilkins, Inc.

The Progress and Challenges of the e-Government Initiatives and Implementation in the Kurdistan Region of Iraq

The Electronic Government (e-Government) means delivering the services and information to the citizens and businesses through the use of Information and Communication Technology (ICT) in order to enable them to interact more effectively with the government, and to increase the quality of the services. As many other governments in the developed and developing countries, the Kurdistan Regional Government (KRG) has embarked on the e-Government initiatives. This study revealed that there are various challenges which affect the e-Government in the Kurdistan Region of Iraq (KRI), but also a lot of e-Government progress has happened. In addition, based on the United Nations’ e-Government maturity level benchmarking, the e-Government in the KRI is at the interactive stage. In this study the services that the citizens want from the government in order to implement an appropriate e-Government were also identified.

New and Emerging Challenges of the ICT-Mediated Health and Well-Being Services

This monograph dissertation looks into the field of ICT-mediated health and well-being services. Through six chapters that extend the work done in the reviewed and published articles, the dissertation focuses on new and emerging technologies, and to impact of their use on the beneficiary; the individual who eventually derives advantage from the services. As the field is currently going through major changes particularly in the OECD countries, the focus is on shortterm developments in the field and the analysis on the long term developments is cursory by nature. The dissertation includes theoretical and empirical elements. Most of the empirical elements are linked to product development and conceptualization performed in the national MyWellbeing project that ended in 2010. In the project, the emphasis was on conceptualization of a personal aid for the beneficiary that could be used for managing information and services in the field of health and well-being services. This work continued the theme of developing individual-centric solutions for the field; a work that started in the InnoElli Senior program in 2006. The nature of this thesis is foremost a conceptual elaboration based on a literature review, illustrated in empirical work performed in different projects. As a theoretical contribution, this dissertation elaborates the role of a mediator, i.e. an intermediary, and it is used as an overarching theme. The role acts as a ‘lens’ through which a number of technology-related phenomena are looked at, pinned down and addressed to a degree. This includes introduction of solutions, ranging from anthropomorphic artefacts to decision support systems that may change the way individuals experience clinical encounters in the near-future. Due to the complex and multiform nature of the field, it is impractical and effectively impossible to cover all aspects that are related to mediation in a single work. Issues such as legislation, financing and privacy are all of equal importance. Consideration of all these issues is beyond the scope of this dissertation and their investigation is left to other work. It follows from this that the investigation on the role is not intended as inclusive one. The role of the mediator is also used to highlight some of the ethical issues related to personal health information management, and to mediating health and well-being related issues on behalf of another individual, such as an elderly relative or a fellow member of a small unit in the armed forces. The dissertation concludes in a summary about the use and functions of the mediator, describing some potential avenues for implementing such support mechanisms to the changing field of ICT-mediated health and well-being services. The conclusions also describe some of the limitations of this dissertation, including remarks on methodology and content.

Virtual Cellar of the Estonian Literary Museum: the Challenges of the Open Access in the Digital Era

Poster at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Educating for Community Resilience: How the Work of Thomas Homer-Dixon and JohnDewey's Pattern of Inquiry Can Help Us Prepare for the Ecological and Social Challenges of the 21st Century

Scientists have overwhelmingly concluded that global warming occurs as a consequence of human activities and that climate change, combined with the depletion of resources, could have catastrophic consequences for the human civilization later this century. However, in political circles and in the public sphere these conclusions are not taken seriously, or they are laid aside for future generations to deal with; at the same time, significant efforts are being deployed to discredit the scientific evidence. In this thesis I have studied the positions of climate scientists as well as those of climate change deniers, and I also examined how their points of view are likely to impact the interests and habits of corporations and citizens. The work of Thomas Homer-Dixon was used as an important source for analyzing the complex interaction between our natural, economic, and social systems, and John Dewey's pattern of inquiry provided the theoretical foundation for an analysis of the current crisis and its possible solutions. No concerted action to deal with climate change has yet been taken by the leaders of the Western world; I corroborated data from four reliable sources (Hansen, 2009; IPCC, 2007; Lynas, 2007; Steffen, 2011) regarding several development scenarios and their likely consequences on greenhouse gas emissions, and I concluded that a future temperature increase of more than 2°C appears now as unavoidable. In the light of this conclusion I argue that education for increasing the resilience of smaller communities is a realistic alternative that can offer some hope in dealing with the challenges ahead.

Challenges of the accession of Turkey into the European Union

Turkey's accession to the European Union (EU) has become, over the years, one of the most contentious issues of European integration. On October 3rd 2005, the European Commission began negotiations for its accession, and, although they will probably not be completed within a decade, its objective is the full accession to the Union. Turkey's accession to the EU presents challenges for both parties, but especially for the European Union. There are very different challenges from the previous accessions, indeed. This work aims to analyze the challenges the EU will face towards Turkey's possible accession to the European Community. Therefore, this work has been divided into three sections. In the first of them, entitled "Brief history of a complex negotiation", the negotiation is briefly described. The second, "Aspects to take into account for Turkey's accession to the European Union", in which different relevant (geopolitical, economic and financial, demographic, cultural and religious) aspects of the possible a cession are discussed: aspects that will have an important impact in the development and performance of the European Community, once accession is fulfilled. The third and last section, "Turkey's incorporating challenges", discusses the challenges the EU will have to face with the potential accession of Turkey, specifically concerning four dimensions: institutional capacity, regional and cohesion policy, EU common security and foreign policy.