The DART-Europe project: towards developing a European theses portal

This paper will report on the new European theses project DART-Europe. The purpose of this project is to align institutional and national e-theses developments across Europe with the wider open archives movement by the construction of a European portal for research theses, thus enabling a global view of European institutional research assets. This project is driven through an innovative partnership between an information provider and an international body of university libraries and open access consortia. The project’s goal is to explore the creation of a European model for the deposit, discovery, use and long-term care of research theses in an open access environment. The paper will outline the projected outcomes of DART-Europe, which is an active group of institutions in addition to a technical service. To this end, DART-Europe is engaged with disciplines and institutions that are widening the definition of research by redefining the formats of theses. For institutions and countries without a repository infrastructure, DART-Europe will enable the creation of a depository. Institutions and countries with a repository infrastructure can engage with DART-Europe to deliver their e-theses. DART-Europe acts as a technology bridge for researchers between those who have existing infrastructures and those who do not. The DART-Europe architecture assumes free at point of use access to full text theses, whether held on the DART-Europe server or by institutional repositories. This paper will provide session attendees with the current progress of this initiative, including a report on the 5 strands of the project, including: architecture; creation of a management tool kit; content acquisition; digital preservation and an investigation of business models

Sleeve Gastrectomy Leads to Weight Loss in the Magel2 Knockout Mouse

Background Prader-Willi syndrome (PWS) is a genetic disorder characterized by hyperphagia, obesity, cardiopulmonary diseases, and increased mortality. Although successful weight loss improves health in PWS, few treatments cause sustained weight loss in obese patients let alone obese individuals with PWS. Objectives The present study uses the Magel2 knockout (KO) mouse, an animal model of PWS, to conduct a preclinical study on the efficacy of sleeve gastrectomy(SG) in PWS. Setting Academic research laboratory, United States. Methods We performed sham or SG surgeries in 24- to 28-week-old male Magel2 KO and wild-type littermate control mice (WT) who had been maintained on a high-fat diet for 10 weeks. We monitored weight, food intake, and fat and lean mass pre- and postoperatively. Fasting glucose, glucose tolerance, and counter-regulation were measured postoperatively. Results Magel2 KO animals had similar recovery and mortality rates compared with WT. SG resulted in similar weight loss, specifically loss of fat but not lean mass, in both Magel2 KO and WT mice. SG also resulted in significantly lower fasting glucose levels and a reduction in fat intake in both Magel2 KO and WT mice. We also found that Magel2 KO mice failed to increase their food intake in response to the glucoprivic agent 2-deoxy-D-glucose, suggesting impaired glucose counter-regulation, but this occurred regardless of surgical status. All results were considered significant when P\u3c .05. Conclusion We find in this mouse model of PWS, SG is a well-tolerated, effective strategy for weight and fat loss

Public-Private Partnerships in the Water Sector

Public-private partnerships (PPPs) have grown in popularity as a method to leverage private-sector actors in the production of government services. With the global challenge of water insecurity, PPPs are becoming more common for large-scale water infrastructure projects such as desalination. Desalination facilities are complex and expensive operations, which means that understanding the appropriate context for PPPs is increasingly important. To understand how different PPP arrangements are used in the water sector, a team of researchers at Texas A&M University examined the global desalination sector and select cities around the world using PPPs for desalination. This brief summarizes what they learned about how risks are shared between the private and public sector, how those risks vary globally, and current trends in water infrastructure finance

Treatment of interictal epileptiform discharges can improve behavior in children with behavioral problems and epilepsy

Objectives: It is generally agreed that children should be treated for epilepsy only if they have clinical seizures. The aim of this study was to examine whether suppressing interictal discharges can affect behavior in children with epilepsy.// Study design: In a double-blinded, placebo-controlled, crossover study, 61 children with well-controlled or mild epilepsy were randomly assigned to add-on therapy with either lamotrigine followed by placebo or placebo followed by lamotrigine. Ambulatory electroencephalographic recordings and behavioral scales were performed during baseline and at the end of placebo and drug phases. The primary hypothesis to be tested was that behavioral scales would improve specifically in patients with a reduction of electroencephalographic discharges during active drug treatment.// Results: Global rating of behavior significantly improved only in patients who showed a significant reduction in either frequency (P < .05) or duration of discharges (P < .05) during active treatment but not in patients with without a significant change in discharge rate. This improvement was mainly seen in patients with partial epilepsy (P < .005).// Conclusions: Our data suggest that suppressing interictal discharges can improve behavior in children with epilepsy and behavioral problems, particularly partial epilepsy. Focal discharges may be involved in the underlying mechanisms of behavioral problems in epilepsy

Barriers to adherence in adolescents and young adults with cystic fibrosis: a questionnaire study in young patients and their parents

Vibeke Bregnballe1, Peter Oluf Schi&amp;oslash;tz1, Kirsten A Boisen2, Tacjana Pressler3, Mikael Thastum4 1Department of Paediatrics, Aarhus University Hospital, Aarhus, Denmark; 2Centre of Adolescent Medicine, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark; 3Cystic Fibrosis Centre, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark; 4Department of Psychology, University of Aarhus, Aarhus, Denmark Background: Treatment adherence is crucial in patients with cystic fibrosis, but poor adherence is a problem, especially during adolescence. Identification of barriers to treatment adherence and a better understanding of how context shapes barriers is of great importance in the disease. Adolescent reports of barriers to adherence have been studied, but studies of their parents&amp;#39; experience of such barriers have not yet been carried out. The aim of the present study was to explore barriers to treatment adherence identified by young patients with cystic fibrosis and by their parents. Methods: A questionnaire survey of a cohort of young Danish patients with cystic fibrosis aged 14&amp;ndash;25 years and their parents was undertaken. Results: Barriers to treatment adherence were reported by 60% of the patients and by 62% of their parents. Patients and parents agreed that the three most common barriers encountered were lack of time, forgetfulness, and unwillingness to take medication in public. We found a significant positive correlation between reported number of barriers and perceived treatment burden. We also found a statistically significant relationship between the reported number of barriers and treatment adherence. A significant association was found between the number of barriers and the reactions of adolescents/young adults and those of their mothers and fathers, and between the number of barriers and the way the family communicated about cystic fibrosis. Conclusion: The present study showed that the majority of adolescents with cystic fibrosis and their parents experienced barriers to treatment adherence. Agreement between adolescents and their parents regarding the level and types of barriers indicates an opportunity for close cooperation between adolescents, their parents, and health care professionals in overcoming adolescent adherence problems. Keywords: cystic fibrosis, adolescents, parents, barriers, adherenc

The Melanocortin-4 Receptor Integrates Circadian Light Cues and Metabolism

The melanocortin system directs diverse physiological functions from coat color to body weight homoeostasis. A commonality among melanocortin-mediated processes is that many animals modulate similar processes on a circannual basis in response to longer, summer days, suggesting an underlying link between circadian biology and the melanocortin system. Despite key neuroanatomical substrates shared by both circadian and melanocortin-signaling pathways, little is known about the relationship between the two. Here we identify a link between circadian disruption and the control of glucose homeostasis mediated through the melanocortin-4 receptor (Mc4r). Mc4r-deficient mice exhibit exaggerated circadian fluctuations in baseline blood glucose and glucose tolerance. Interestingly, exposure to lighting conditions that disrupt circadian rhythms improve their glucose tolerance. This improvement occurs through an increase in glucose clearance by skeletal muscle and is food intake and body weight independent. Restoring Mc4r expression to the paraventricular nucleus prevents the improvement in glucose tolerance, supporting a role for the paraventricular nucleus in the integration of circadian light cues and metabolism. Altogether these data suggest that Mc4r signaling plays a protective role in minimizing glucose fluctuations due to circadian rhythms and environmental light cues and demonstrate a previously undiscovered connection between circadian biology and glucose metabolism mediated through the melanocortin system

Successful private–public funding of paediatric medicines research: lessons from the EU programme to fund research into off-patent medicines

The European Paediatric Regulation mandated the European Commission to fund research on off-patent medicines with demonstrated therapeutic interest for children. Responding to this mandate, five FP7 project calls were launched and 20 projects were granted. This paper aims to detail the funded projects and their preliminary results. Publicly available sources have been consulted and a descriptive analysis has been performed. Twenty Research Consortia including 246 partners in 29 European and non-European countries were created (involving 129 universities or public funded research organisations, 51 private companies with 40 SMEs, 7 patient associations). The funded projects investigate 24 medicines, covering 10 therapeutic areas in all paediatric age groups. In response to the Paediatric Regulation and to apply for a Paediatric Use Marketing Authorisation, 15 Paediatric Investigation Plans have been granted by the EMAPaediatric Committee, including 71 studies of whom 29 paediatric clinical trials, leading to a total of 7,300 children to be recruited in more than 380 investigational centres. Conclusion: Notwithstanding the EU contribution for each study is lower than similar publicly funded projects, and also considering the complexity of paediatric research, these projects are performing high-quality research and are progressing towards the increase of new paediatric medicines on the market. Private–public partnerships have been effectively implemented, providing a good example for future collaborative actions. Since these projects cover a limited number of offpatent drugs and many unmet therapeutic needs in paediatrics remain, it is crucial foreseeing new similar initiatives in forthcoming European funding programmes

Associations between adherence, depressive symptoms and health-related quality of life in young adults with cystic fibrosis

BACKGROUND: Cystic fibrosis (CF) is a life shortening disease, however prognosis has improved and the adult population is growing. Most adults with cystic fibrosis live independent lives and balance the demands of work and family life with a significant treatment burden. The aim of this study was to examine the relationships among treatment adherence, symptoms of depression and health-related quality of life (HRQoL) in a population of young adults with CF. METHODS: We administered three standardized questionnaires to 67 patients with CF aged 18–30 years; Morisky Medication Adherence Scale, Major Depression Inventory, and Cystic Fibrosis Questionnaire-Revised. RESULTS: There was a response rate of 77 % and a majority of the young adults (84 %) were employed or in an education program. Most participants (74 %) reported low adherence to medications. One third (32.8 %) of the participants reported symptoms of depression. HRQoL scores were especially low on Vitality and Treatment Burden, and symptoms of depression were associated with low HRQoL scores (p < 0.01) with medium to large deficits across on all HRQoL domains (Cohen’s d 0.60–1.72) except for the domain treatment burden. High depression symptom scores were associated with low adherence (r = −0.412, p < 0.001). CONCLUSIONS: Despite improved physical health, many patients with CF report poor adherence, as well as impaired mental wellbeing and HRQoL. Thus, more attention to mental health issues is needed

Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection

Chronic lung infection by Pseudomonas aeruginosa is the major severe complication in cystic fibrosis (CF) patients, where P. aeruginosa persists and grows in biofilms in the endobronchial mucus under hypoxic conditions. Numerous polymorphonuclear leukocytes (PMNs) surround the biofilms and create local anoxia by consuming the majority of O2 for production of reactive oxygen species (ROS). We hypothesized that P. aeruginosa acquires energy for growth in anaerobic endobronchial mucus by denitrification, which can be demonstrated by production of nitrous oxide (N2O), an intermediate in the denitrification pathway. We measured N2O and O2 with electrochemical microsensors in 8 freshly expectorated sputum samples from 7 CF patients with chronic P. aeruginosa infection. The concentrations of NO 3- and NO2- in sputum were estimated by the Griess reagent. We found a maximum median concentration of 41.8 μM N2O (range 1.4-157.9 μM N2O). The concentration of N2O in the sputum was higher below the oxygenated layers. In 4 samples the N2O concentration increased during the initial 6 h of measurements before decreasing for approximately 6 h. Concomitantly, the concentration of NO3- decreased in sputum during 24 hours of incubation. We demonstrate for the first time production of N2O in clinical material from infected human airways indicating pathogenic metabolism based on denitrification. Therefore, P. aeruginosa may acquire energy for growth by denitrification in anoxic endobronchial mucus in CF patients. Such ability for anaerobic growth may be a hitherto ignored key aspect of chronic P. aeruginosa infections that can inform new strategies for treatment and prevention. © 2014 Kolpen et al

Micronutrient Deficiency Independently Predicts Time to Event in Patients with Heart Failure

Background—Dietary micronutrient deficiencies have been shown to predict event‐free survival in other countries but have not been examined in patients with heart failure living in the United States. The purpose of this study was to determine whether number of dietary micronutrient deficiencies in patients with heart failure was associated with shorter event‐free survival, defined as a combined end point of all‐cause hospitalization and death. Methods and Results—Four‐day food diaries were collected from 246 patients with heart failure (age: 61.5±12 years; 67% male; 73% white; 45% New York Heart Association [NYHA] class III/IV) and analyzed using Nutrition Data Systems for Research. Micronutrient deficiencies were determined according to methods recommended by the Institute of Medicine. Patients were followed for 1 year to collect data on all‐cause hospitalization or death. Patients were divided according to number of dietary micronutrient deficiencies at a cut point of ≥ 7 for the high deficiency category versus \u3c 7 for the no to moderate deficiency category. In the full sample, 29.8% of patients experienced hospitalization or death during the year, including 44.3% in the high‐deficiency group and 25.1% in the no/moderate group. The difference in survival distribution was significant (log rank, P = 0.0065). In a Cox regression, micronutrient deficiency category predicted time to event with depression, NYHA classification, comorbidity burden, body mass index, calorie and sodium intake, and prescribed angiotensin‐converting enzyme inhibitors, diuretics, or β‐blockers included as covariates. Conclusions—This study provides additional convincing evidence that diet quality of patients with heart failure plays an important role in heart failure outcomes