Pharmacological inhibition of interleukin-15 prevents colitis and associated bone loss in IL-10 knockout mice

Bone loss secondary to inflammatory bowel diseases (IBD) is largely explained by activated T cells producing cytokines that trigger osteoclastogenesis and accelerate bone resorptionwhile inhibiting bone formation. In IBD, elevated expression of interleukin (IL)-15, a T cell growth factor, plays a central role in T cell activation, pro-inflammatory cytokine production and the development of colitis. We previously reported that IL-15 enhances RANKL-induced osteoclastogenesis and that an IL-15 antagonist, CRB-15, prevents weight and bone loss in a mousemodel of dextran sulfate sodium-induced colitis.We hypothesized that inhibition of IL-15 signalingmight prevent bone loss in IL-10 deficient (IL10−/−) mice, that develop spontaneous bowel inflammation associatedwith osteopeniawhen they are no longer raised under germ-free conditions.Mice received anIL-15 antagonist (CRB-15, 5 μg/day, n=5) or IgG2a (5 μg/day, n=4) fromweek 10 to 14 of age. The severity of colitis was assessed by histology and bowel cytokine gene expression by real time PCR. Bone mass and architecturewere evaluated by ex vivo DXA on femur and micro-computed tomography on femur and vertebra. Bodyweight gainwas similar in the two groups. After 4 weeks, colonwas 29% shorter in CRB-15 treatedmice (p<0.006), a sign of reduced inflammation. Histological analysis indicated a transmural infiltration of inflammatory cells, lymphoepithelial lesions and increased size of villi (histological score=4/6) in IgG2a treated mice, whereas colon from CRB-15 treated mice exhibited mild infiltration of inflammatory cells of the lamina propria, no mucosal damages and a minimal increased size of villi (histological score=1.6/6). Levels of TNFα, IL-17 and IL-6 mRNA in the colon were significantly reduced in CRB-15 treated mice (p<0.04 vs IgG2), indicating a decrease in colon inflammation. CRB-15 improved femur BMD (+10.6% vs IgG2a, p<0.002), vertebral trabecular bone volume fraction (BV/TV, +19.7% vs IgG2a, p<0.05) and thickness (+11.6% vs IgG2a, p<0.02). A modest but not significant increase in trabecular BV/TV was observed at the distal femur. Cortical thicknesswas also higher at themidshaft femur in CRB-15 treatedmice (+8.3% vs IgG2a, p<0.02). In conclusion, we confirm and extend our results about the effects of CRB-15 in colitis. Antagonizing IL-15 may exert favorable effects on intestinal inflammation and prevent bone loss and microarchitecture alterations induced by colitis. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: B. Brounais-Le Royer Grant / Research Support from Novartis Consumer Health Foundation, S. Ferrari-Lacraz: none declared, D. Velin: none declared, X. Zheng: none declared, S. Ferrari: none declared, D. Pierroz: none declared.

Weigh2go: A Peripatetic Level 1 Weight Management Service

The aim of this intervention is to increase the accessibility of appropriate evidence based support to people who are clinically obese to enable them to make lifestyle changes that will lead to weight loss. Objectives1. Identify patients whose lifestyle put them at risk of obesity and poor health outcomes and provide them with advice and support along with signposting to specific services and activities. 2. Identify patients who are overweight or obese and offer them a structured multi-component programme of support for them to loose weight. 3. Through the use of software collect data to monitor outcomes at individual and practice levels.

A Study of the Epidemiology of AIDS in Ireland and an Evaluation of an AIDS Education Programme in Second-level Schools

Second-level school students have been identified by the Minister for health as a priority group for education on AIDS. An education programme was accordingly initiated in 1988 in Community Care Area 1 in South county Dublin. This report evaluates this education intervention by means of pre- and post- intervention questionnaires. The questionnaire examined knowledge and attitudes of students relevant to AIDS. The results showed that the level of knowledge of students living in this area was high prior to intervention. The education programme succeeded in improving some aspects of knowledge and also influenced some attitudes of the students. A study of the epidemiology of Aids in Ireland reveals that the epidemic is at a relatively early stage with a consequent rapid doubling time of 9-10 months. In comparison with most developed countries Ireland has a high proportion of AIDS cases occurring among intravenous drug abusers and directly related to this a high number of HIV infected children. Examination of the literature reveals that behaviour change has occurred most noticeably among the homosexual/bisexual risk group. There is some evidence that the comprehensive programmes can achieve change in the behaviour of intravenous drug abusers. There are very few reports linking behaviour change among adolescents and young adults to education programmes. Much of the available literature relates to changes in knowledge and attitudes. International recommendations on the nature of the ideal health education intervention on AIDS are reviewed. The importance of a comprehensive health education programme which incorporates AIDS education and which commences early in youth is noted. The role of the community physician in relation to education programmes and other aspects of monitoring and management of the AIDS epidemic is discussed.This resource was contributed by The National Documentation Centre on Drug Use.

Correlating the end-Triassic mass extinction and flood basalt volcanism at the 100 ka level

New high-precision U/Pb geochronology from volcanic ashes shows that the Triassic-Jurassic boundary and end-Triassic biological crisis from two independent marine stratigraphic sections correlate with the onset of terrestrial flood volcanism in the Central Atlantic Magmatic Province to <150 ka. This narrows the correlation between volcanism and mass extinction by an order of magnitude for any such catastrophe in Earth history. We also show that a concomitant drop and rise in sea level and negative delta C-13 spike in the very latest Triassic occurred locally in <290 ka. Such rapid sea-level fluctuations on a global scale require that global cooling and glaciation were closely associated with the end-Triassic extinction and potentially driven by Central Atlantic Magmatic Province volcanism.

Blood glucose level on postoperative day 1 is predictive of adverse outcomes after cardiovascular surgery.

AIM: Hyperglycaemia is now a recognized predictive factor of morbidity and mortality after coronary artery bypass grafting (CABG). For this reason, we aimed to evaluate the postoperative management of glucose control in patients undergoing cardiovascular surgery, and to assess the impact of glucose levels on in-hospital mortality and morbidity. METHODS: This was a retrospective study investigating the association between postoperative blood glucose and outcomes, including death, post-surgical complications, and length of stay in the intensive care unit (ICU) and in hospital. RESULTS: A total of 642 consecutive patients were enrolled into the study after cardiovascular surgery (CABG, carotid endarterectomy and bypass in the lower limbs). Patients' mean age was 68+/-10 years, and 74% were male. In-hospital mortality was 5% in diabetic patients vs 2% in non-diabetic patients (OR: 1.66, P=0.076). Having blood glucose levels in the upper quartile range (> or =8.8 mmol/L) on postoperative day 1 was independently associated with death (OR: 10.16, P=0.0002), infectious complications (OR: 1.76, P=0.04) and prolonged ICU stay (OR: 3.10, P<0.0001). Patients presenting with three or more hypoglycaemic episodes (<4.1 mmol/L) had increased rates of mortality (OR: 9.08, P<0.0001) and complications (OR: 8.57, P<0.0001). CONCLUSION: Glucose levels greater than 8.8 mmol/L on postoperative day 1 and having three or more hypoglycaemic episodes in the postoperative period were predictive of mortality and morbidity among patients undergoing cardiovascular surgery. This suggests that a multidisciplinary approach may be able to achieve better postoperative blood glucose control.

National Audit of the Organisation of Services for Falls and Bone Health of Older People

This report presents the results of the second national audit which examines the organisation of services provided to older people for falls prevention and bone health. Falls and fractures are a common and serious problem affecting older people, with high levels of personal and financial cost. National guidelines, supported by the research evidence, require the provision of integrated services for falls and fracture prevention and treatment. Effective commissioning is needed to produce such high quality services.��This audit was commissioned by the Healthcare Quality Improvement Partnership (HQIP) as part of the second cycle of audits on services for the prevention of falls and fractures in older people. It follows the first organisational audit, performed in 2005, and the clinical audit of 2007. All were audited against specific standards from the National Service Framework for Older People (NSF) and guidance from the National Institute for Health and Clinical Excellence (NICE). Since the first audit, indicators have been added or updated in line with new guidance including that on falls prevention of inpatients following the National Patient Safety Agency (NPSA) report on slips, trips and falls in hospital (2007). For the first time, the audit also looks specifically at falls and fracture prevention in mental healthcare and a sample of care homes.

Health Inequality Profiles 2008 - MSOA level data (v2)

Using mortality and population data from 2001 to 2007 DSRs and life expectancy were calculated for all Middle Layer Super Output Areas in the East of England.

Pronostic factors in solitary plasmacytoma of the bone: A Rare Cancer Network study

Contexte Le plasmocytome isolé osseux est une tumeur maligne rare des cellules plasmocytaires. Les données issues de la littérature ne permettent pas de se déterminer sur la dose radiothérapeutique optimale. Dans cette perspective nous avons conduit une vaste étude rétrospective dans le but d'évaluer l'évolution, les facteurs pronostiques aunsi que la dose radiothérapeutique optimale chez les patients présentant un plasmocytome isolé. Méthodes Nous avons réunis les données de 206 patients présentant un plasmocytome isolé osseux sans évidence de myélome multiple. Chaque cas a été documenté histopathologiquement. La majorité des patients (n=169) ont été traités par radiothérapie seule, 32 par une combinaison radiothérapie-chimiothérapie, et 5 par chirurgie. La durée de suivi médiane fut de 54 mois (7-245) Résultats A 5 ans, la survie globale est de 70%, la survie sans maladie de 46% et le contrôle local de 88%. La durée médiane de développement vers une myélome multiple est de 21 mois (2-135) avec une probabilité à 5 ans de 51 %. Les analyses multivariées indiquent l'âge (<60 ans) et la taille de la tumeur (<5cm) comme facteur favorables pour survie. L'âge (<60ans) se dégage comme facteur favorable pour la survie sans maladie. La localisation de la tumeur (vertébrale vs autre) indique la probabilité de contrôle local. L'âge plus avancé (>60 ans) est le seul prédicteur de myélome multiple. Aucune relation dose-réponse n'est mise en évidence pour les doses supérieures à 30 Gy, même pour lés tumeurs les plus étendues. Conclusions Les patients les plus jeunes, principalement ceux présentant une localisation vertébrale, présentent la meilleure évolution sous traitement radiothérapeutique modéré. La progression vers le myélome multiple reste le problème thérapeutique principal. Les futures investigations devraient se focaliser sur les chimiothérapies adjuvantes ainsi que sur les nouveaux agents thérapeutiques.

Postmortem findings in bone cement implantation syndrome-related deaths.

Several mechanisms have been postulated as potentially involved in life-threatening complications during cemented surgery. In this study, we evaluated the role of anaphylaxis and pulmonary fat embolism in the pathophysiology of bone cement implantation syndrome in a series of fatal cases that underwent medicolegal investigations. Postmortem findings in these cases were compared with those obtained from individuals who died after other injuries and/or interventions and in which activated mast cells and pulmonary fat embolism were involved in the pathogenesis of death. Fifty subjects were selected including 6 individuals who had undergone cemented total hip arthroplasty and died intraoperatively, 32 subjects who died shortly after being involved in traffic accidents, 8 individuals who died shortly after the injection of contrast material, and 4 subjects who had undergone orthopedic surgery and died postoperatively. Massive pulmonary fat embolism was determined to be the cause of death in all the 6 subjects who died intraoperatively as well as the main cause of death in traffic-road victims with rapid respiratory function deterioration. Mast cell activation was identified exclusively in the group of subjects who died shortly after contrast material administration. Massive pulmonary fat embolism appears to be the most important factor responsible for severe cardiorespiratory function deterioration during cemented arthroplasty. Cardiac comorbidities can also significantly influence the severity of intraoperative complications, thus corroborating the hypothesis of a multifactorial model in the pathogenesis of bone cement implantation syndrome.

Uncertainty about the true source. A note on the likelihood ratio at the activity level.

This paper focuses on likelihood ratio based evaluations of fibre evidence in cases in which there is uncertainty about whether or not the reference item available for analysis - that is, an item typically taken from the suspect or seized at his home - is the item actually worn at the time of the offence. A likelihood ratio approach is proposed that, for situations in which certain categorical assumptions can be made about additionally introduced parameters, converges to formula described in existing literature. The properties of the proposed likelihood ratio approach are analysed through sensitivity analyses and discussed with respect to possible argumentative implications that arise in practice.

Addressing High Level ICT Skills Recruitment Needs

Ireland is a successful major centre for ICT operations with ten of the top ICT companies in the world having substantial operations here. The large talent pool of ICT professionals that exists here is valuable both for foreign-owned and Irish companies. The cluster of internationally renowned firms and Irish companies offer a range of attractive career opportunities for professionals. A range of skills recruitment difficulties have been raised through the work of the Expert Group on Future Skills Needs (EGFSN), specifically the immediate issue of high-level ICT skills within both the ICT sector and from other sectors such as international financial services, banking and business services. Forfs, with the support of IDA Ireland and Enterprise Ireland, engaged in discussions with a selected range of foreign–owned and Irish companies employing approximately 30,000 employees to establish the nature of positions involved, the reasons for recruitment difficulties and to identify measures to help address them. Consultations were also held with key stakeholders including IDA Ireland, Enterprise Ireland, ICT Ireland, Software Ireland, IT@Cork, Engineers Ireland and Dublin Chambers of Commerce. Discussions were held with the heads of the computing departments of all Universities and Institutes of Technology at a meeting chaired by the Higher Education Authority. An in-depth analysis of third-level ICT supply statistics and trends was undertaken to inform the research.

ICT Action Plan Meeting the high-level skills needs of enterprise in Ireland

The technology sector in Ireland is thriving. Employment, through indigenous and multinational technology firms continues to grow strongly year on year. All of the top 10 multinational technology companies have a significant presence in Ireland and the indigenous software sector’s exports are worth well in excess of €1 billion annually. Five of the top 10 exporters in Ireland are technology companies, and the sector is responsible for approximately one-third of Ireland’s total turnover. Since January 2011, over 80 jobs a week have been announced in the sector. This is on foot of 6% employment growth in 2009 and 4% in 2010. A recent global competitiveness report ranks Ireland as the top destination in the world by quality and value of investments. With a growing multinational technology presence in Ireland and a vibrant and innovative indigenous software sector, the future prospects for Ireland’s technology sector are bright.

Naming the Reformed Junior Cycle Proposals for the Minister for Education and Skills - Irish Second Level Students Union (ISSU)

It was important to us to engage with as many students as possible throughout the process of developing a new name for the reformed junior cycle. In this vein, we used a wide variety of methods to engage with students in order to capture as many ideas as possible; text messaging, Facebook, Twitter, email and consultation sessions. We circulated posters to all schools via post and/or email, and contacted schools in catchment areas for the consultation sessions by phone. In our consultation sessions, we had discussions with the participating students about what the new junior cycle would be, closely guided by the content of “Towards a Framework for Junior Cycle” from the National Council for Curriculum and assessment. In these sessions, students then gave feedback on what they thought of the reformed junior cycle, developed their own ideas, and identified what they thought should be reflected in the name of the reformed junior cycle

Report of the Action Group on Access to Third Level Education

In line with a commitment under the Programme for Prosperity and Fairness the Minister for Education and Science, Dr Michael Woods, established the Action Group on Access to Third Level Education, in September 2000, to advise the Minister on the development of a co-ordinated framework to promote access by mature and disadvantaged students and students with disabilities to third level education.

Supporting A Better Transition From Second Level To Higher Education: Key directions and Next Steps

Supporting A Better Transition From Second Level To Higher Education. Provided by the Department of Education and Skills, Ireland.