Report of the National Advisory Committee on Palliative Care

Report of the National Advisory Committee on Palliative Care It is anticipated that the need for palliative care services will increase in coming years. Population projections indicate that between 1996 and 2031 the population aged 65 years and over is expected to more than double. Currently, over 95% of all patients availing of palliative care services suffer from cancer. The number of people dying from cancer is expected to rise in future years, due to the ageing population. Click here to download the document (PDF, 1mb)

Seeds of hope: Assessing the effect of development aid on the reduction of child mortality

The Millennium Declaration (2000) set as one of its targets a substantial reduction in child mortality. This paper studies whether the massive increase in development aid can account for part of the reduction in child mortality observed in developing countries since the year 2000. To do so, we analyze a panel of more than 130 developing countries over the 2000-2008 period. We use the time trend evolution of aid to identify an exogenous source of variation. Total aid has had no statistically significant effect on child mortality. However, a disaggregate analysis identifies certain sectors of aid that have had a significant impact. The effects have been larger in high mortality countries, including Sub-Saharan Africa. Projections based on our estimates strongly support the concern that most countries in that region will miss the Millennium Goals target on child mortality.

Health and Social Care Implications of Population Ageing In Ireland 1991-2011

This report has two main objectives. The first is to set out national and health board area population projections for Ireland in the period 1991-2011, with special reference to the elderly population. The second is to consider the implications of the predicted trends in the elderly population for health and social care services over the same period, taking account of official policy objectives and service norms for the health services. Download the Report here

Where will conflicts between alien and rare species occur after climate and land-use change? A test with a novel combined modelling approach

Protecting native biodiversity against alien invasive species requires powerful methods to anticipate these invasions and to protect native species assumed to be at risk. Here, we describe how species distribution models (SDMs) can be used to identify areas predicted as suitable for rare native species and also predicted as highly susceptible to invasion by alien species, at present and under future climate and land-use scenarios. To assess the condition and dynamics of such conflicts, we developed a combined predictive modelling (CPM) approach, which predicts species distributions by combining two SDMs fitted using subsets of predictors classified as acting at either regional or local scales. We illustrate the CPM approach for an alien invader and a rare species associated to similar habitats in northwest Portugal. Combined models predict a wider variety of potential species responses, providing more informative projections of species distributions and future dynamics than traditional, non-combined models. They also provide more informative insight regarding current and future rare-invasive conflict areas. For our studied species, conflict areas of highest conservation relevance are predicted to decrease over the next decade, supporting previous reports that some invasive species may contract their geographic range and impact due to climate change. More generally, our results highlight the more informative character of the combined approach to address practical issues in conservation and management programs, especially those aimed at mitigating the impact of invasive plants, land-use and climate changes in sensitive regions

Tackling Chronic Disease - A Policy Framework for the Management of Chronic Diseases

Tackling Chronic Disease – A Policy Framework for the Management of Chronic Diseases Chronic diseases are recognised as a major health challenge. In the healthcare system, they represent the major component of service activity and expenditure, as well as the major contributor to mortality and ill-health in this country. Given the population projections which predict a doubling of the elderly population over the next 30 years, this will give rise to a significant increase in chronic diseases with the consequent burden on society, the healthcare system and individuals. Click here to download PDF 1.8mb

Supplementary Report of the HIA to the Minister for Health, in accordance with Section 7E(1)(b) of the Health Insurance Acts, 1994-2009 (Redacted Version)

The purpose of this Supplementary Report is to advise on how the budgetary measures impact on the conclusions in relation to tax credits and stamp duty included in the Authority’s November 2011 Report. in doing so, we will assess the direct impacts and we will discuss some scenarios. However, the Authority’s advice in this area relies on projections of the health insurance market and, in light of the above, there is considerable uncertainty surrounding any projections of how claims inflation or the market size may develop, even in the short and medium terms. Supplementary Report of the HIA to the Minister for Health, in accordance with Section 7E(1)(b) of the Health Insurance Acts, 1994-2009 (Redacted Version) Click here to download PDF 3.2mb

Climate change impact on biodiversity in Switzerland: a review. Journal for Nature Conservation

A noticeable increase in mean temperature has already been observed in Switzerland and summer temperatures up to 4.8 K warmer are expected by 2090. This article reviews the observed impacts of climate change on biodiversity and consider some perspectives for the future at the national level. The following impacts are already evident for all considered taxonomic groups: elevation shifts of distribution toward mountain summits, spread of thermophilous species, colonisation by new species from warmer areas and phenological shifts. Additionally, in the driest areas, increasing droughts are affecting tree survival and fish species are suffering from warm temperatures in lowland regions. These observations are coherent with model projections, and future changes will probably follow the current trends. These changes will likely cause extinctions for alpine species (competition, loss of habitat) and lowland species (temperature or drought stress). In the very urbanised Swiss landscape, the high fragmentation of the natural ecosystems will hinder the dispersal of many species towards mountains. Moreover, disruptions in species interactions caused by individual migration rates or phenological shifts are likely to have consequences for biodiversity. Conversely, the inertia of the ecosystems (species longevity, restricted dispersal) and the local persistence of populations will probably result in lower extinction rates than expected with some models, at least in 21st century. It is thus very difficult to estimate the impact of climate change in terms of species extinctions. A greater recognition by society of the intrinsic value of biodiversity and of its importance for our existence will be essential to put in place effective mitigation measures and to safeguard a maximum number of native species.

Director of Public Health annual report 2011 and core tables 2010

Too many children and young people are living in circumstances that make it difficult for them to thrive. That is the key message from the third Annual Report of the Director of Public Health (DPH) for Northern Ireland, which was published on 14th June 2012. This significant report highlights the many public health challenges that affect people in Northern Ireland.As Director of Public Health, Dr Carolyn Harper's report describes the main public health challenges across Northern Ireland, and details work being undertaken by the Public Health Agency (PHA) and its partners over the past year to improve the health and wellbeing of people here.A Core Tables report for 2010, available below, produced by the PHA in support of the Director of Public Health's Annual Report for 2011-2012, including information such as estimated home population figures and projections, births information, fertility rates, death rates, information on mortality, life expectancy, immunisation rates and screening uptake rates.

Director of Public Health annual report 2012 and core tables 2011

Improving the health and wellbeing of the elderly is the theme of the fourth Director of Public Health annual report, launched on 12 June 2013. Northern Ireland's elderly population is growing and older people are living longer than ever before, which emphasises the importance of providing health and social care that allows them to live a productive life.This report highlights the many areas of public health work aimed at giving elderly people in Northern Ireland the best opportunity to live active and healthy lives in a safe and secure environment. An in-depth overview also provides statistics on many aspects of life as an elderly person here - life expectancy, mortality, mental wellbeing, lifestyle, social determinants of health etc. Further, more detailed, data is included in an accompanying report available�as a separate document.��The core tables for 2011, also available to download below, include information such as estimated home population figures and projections, birth rates, fertility rates, death rates, information on mortality, life expectancy, immunisation rates and screening uptake rates.The presentation slides from key speakers from the launch event on 12 June 2013 and all parallel sessions are also appended below.�Please note:�The PHA cannot be held responsible for any breach of copyright that may exist within individual presentations.Anyone wishing to get a copy of the presentation by Ron McDowell�in the 'Identifying those at risk' category should contact him directly at mcdowell-R3@email.ulster.ac.uk

Perfusion measurement in brain gliomas with intravoxel incoherent motion MRI.

BACKGROUND AND PURPOSE: Intravoxel incoherent motion MRI has been proposed as an alternative method to measure brain perfusion. Our aim was to evaluate the utility of intravoxel incoherent motion perfusion parameters (the perfusion fraction, the pseudodiffusion coefficient, and the flow-related parameter) to differentiate high- and low-grade brain gliomas. MATERIALS AND METHODS: The intravoxel incoherent motion perfusion parameters were assessed in 21 brain gliomas (16 high-grade, 5 low-grade). Images were acquired by using a Stejskal-Tanner diffusion pulse sequence, with 16 values of b (0-900 s/mm(2)) in 3 orthogonal directions on 3T systems equipped with 32 multichannel receiver head coils. The intravoxel incoherent motion perfusion parameters were derived by fitting the intravoxel incoherent motion biexponential model. Regions of interest were drawn in regions of maximum intravoxel incoherent motion perfusion fraction and contralateral control regions. Statistical significance was assessed by using the Student t test. In addition, regions of interest were drawn around all whole tumors and were evaluated with the help of histograms. RESULTS: In the regions of maximum perfusion fraction, perfusion fraction was significantly higher in the high-grade group (0.127 ± 0.031) than in the low-grade group (0.084 ± 0.016, P < .001) and in the contralateral control region (0.061 ± 0.011, P < .001). No statistically significant difference was observed for the pseudodiffusion coefficient. The perfusion fraction correlated moderately with dynamic susceptibility contrast relative CBV (r = 0.59). The histograms of the perfusion fraction showed a "heavy-tailed" distribution for high-grade but not low-grade gliomas. CONCLUSIONS: The intravoxel incoherent motion perfusion fraction is helpful for differentiating high- from low-grade brain gliomas.

L'hémisphérotomie péri-insulaire: technique chirurgicale, monitoring EEG intraopératoire et résultats sur le contrôle de l'épilepsie [Periinsular hemispherotomy: surgical technique, intraoperative EEG monitoring and results on seizure outcome]

Peri-insular hemispherotomy is a surgical technique used in the treatment of drug-resistant epilepsy of hemispheric origin. It is based on the exposure of insula and semi-circular sulci, providing access to the lateral ventricle through a supra- and infra-insular window. From inside the ventricle, a parasagittal callosotomy is performed. The basal and medial portion of the frontal lobe is isolated. Projections to the anterior commissure are interrupted at the time of amygdala resection. The hippocampal tail and fimbria-fornix are disrupted posteriorly. We report our experience of 18 cases treated with this approach. More than half of them presented with congenital epilepsy. Neuronavigation was useful in precisely determining the center and extent of the craniotomy, as well as the direction of tractotomies and callosotomy, allowing minimal exposure and blood loss. Intra-operative monitoring by scalp EEG on the contralateral hemisphere was used to follow the progression of the number of interictal spikes during the disconnection procedure. Approximately 90% of patients were in Engel's Class I. We observed one case who presented with transient postoperative neurological deterioration probably due to CSF overdrainage and documented one case of incomplete disconnection in a patient presenting with hemimegalencephaly who needed a second operation. We observed a good correlation between a significant decrease in the number of spikes at the end of the procedure and seizure outcome. Peri-insular hemispherotomy provides a functional disconnection of the hemisphere with minimal resection of cerebral tissue. It is an efficient technique with a low complication rate. Intra-operative EEG monitoring might be used as a predictive factor of completeness of the disconnection and consequently, seizure outcome.

Angiotensin II is an endogenous neurotransmitter for rat and human mesenteric resistance blood vessels

Angiotensin II (Ang II) is one of the most potent vasoconstrictors. We document here the innervation of rat and human mesenteric resistance arteries (MRA) by angiotensinergic neurons of the rat and human sympathetic coeliac ganglia. Angiotensinogen (Ang-N)-mRNA and angiotensin converting enzyme-mRNA but no renin-mRNA were detected by using quantitative real time polymerase chain reaction in total RNA extracts of rat coeliac ganglia. In the same extracts, cathepsin D-mRNA was detected: This protease also cleaves Ang I from Ang-N and could therefore account for the generation of neuronal Ang peptides in the absence of renin. In situ hybridization confirmed the presence of Ang-N-mRNA in the cytoplasm of rat coeliac ganglia. By using solid-phase extraction, high performance liquid chromatography and subsequent radioimmunoassay, Ang II and its metabolites were detected in rat and also in human coeliac ganglia. Immunoreactivity for Ang II was demonstrated in rat and human coeliac ganglia neurons and their projections innervating MRA. In addition, segmental angiotensinergic innervation of MRA was also observed. By means of confocal laser scanning microscopy we were able to demonstrate the presence of angiotensinergic synapses en passant along side of vascular smooth muscle cells. Our findings could indicate that Ang II is synthesized inside the neurons of sympathetic coeliac ganglia and may act as an endogenous neurotransmitter locally in MRA.

Mixing compositions and other scales

Theory of compositional data analysis is often focused on the composition only. However in practical applications we often treat a composition together with covariableswith some other scale. This contribution systematically gathers and develop statistical tools for this situation. For instance, for the graphical display of the dependenceof a composition with a categorical variable, a colored set of ternary diagrams mightbe a good idea for a first look at the data, but it will fast hide important aspects ifthe composition has many parts, or it takes extreme values. On the other hand colored scatterplots of ilr components could not be very instructive for the analyst, if theconventional, black-box ilr is used.Thinking on terms of the Euclidean structure of the simplex, we suggest to set upappropriate projections, which on one side show the compositional geometry and on theother side are still comprehensible by a non-expert analyst, readable for all locations andscales of the data. This is e.g. done by defining special balance displays with carefully-selected axes. Following this idea, we need to systematically ask how to display, explore,describe, and test the relation to complementary or explanatory data of categorical, real,ratio or again compositional scales.This contribution shows that it is sufficient to use some basic concepts and very fewadvanced tools from multivariate statistics (principal covariances, multivariate linearmodels, trellis or parallel plots, etc.) to build appropriate procedures for all these combinations of scales. This has some fundamental implications in their software implementation, and how might they be taught to analysts not already experts in multivariateanalysis

Role of Notch signalling in intestinal epithelium

Résumé: Chez les mammifères, les intestins sont les organes ayant le plus haut taux de renouvellement cellulaire dans l'organisme. L'épithélium intestinal se renouvelle complètement en moins d'une semaine. Il se compose de projections (villosités) et d'invaginations (cryptes) qui ont toutes deux des fonctions bien distinctes. Les cellules de l'intestin sont constamment produites à partir de cellules souches, situées dans la crypte, qui se différencient en cellules proliférantes transitoires, puis en cellules caliciformes, de Paneth, entéroendocrine ou en entérocytes. Ces cellules migrent dans leurs lieux spécifiques pour accomplir leur fonction physiologique pour finalement mourir. A cours de mon travail de thèse, j'ai étudié le rôle de la voie de signalisation de Notch dans le renouvellement cellulaire et dans le processus de l'homéostase des cellules de l'intestin marin en utilisant le système Cre-loxP pour induire la délétion des gènes Notch1, Notch2, Jaggedl et RBP-Jk. Bien que l'inactivation de Notch1 avec ou sans Jagged1, ou celle de Notch2, n'aboutissent à aucun phénotype, une déficience pour RBP-Jk, ou pour Notch1 et Notch2 simultanément, conduit au développement d'un impressionnant phénotype. Au niveau de la crypte, une rapide et importante modification des cellules apparaît: les cellules proliférantes sont devenues des cellules caliciformes qui ont perdu la capacité de se renouveler. Ces résultats impliquent la voie Notch en tant que nouvelle clé de voûte dans le maintien des cellules qui s'auto-renouvellent dans l'épithélium intestinal. Un rôle similaire a été proposé pour la voie Wnt, laquelle n'est cependant, pas affectée dans nos souris. C'est pourquoi ces deux voies sont essentielles dans le maintien de la prolifération dans les cryptes intestinales. Ce travail a aussi proposé un mécanisme par lequel la voie Notch contrôlerait l'intégrité du cycle cellulaire dans les cellules de la crypte intestinale, ceci en inhibant la transcription d'un inhibiteur du cycle cellulaire, la protéine p27KIP1. De plus, l'inactivation de RBP-Jk dans les adénomes développés par les souris APCmin induisent la différenciation de cellules tumorales en cellules caliciformes. Comme autre effet, la localisation histologique des cellules de Paneth est également affectée par la délétion de RBP-Jk ou de Notch1/Notch2, suggérant un rôle pour la voie Notch dans le compartiment des cellules de Paneth. Finalement, ce travail démontre que les cellules progénitrices de l'intestin ont besoin d'une convergence fonctionnelle des voie Wnt et Notch. Ces résultats préliminaires peuvent être considérés comme un concept pour l'utilisation d'inhibiteurs de secrétase-γ (inhibiteurs de Notch) à des fins thérapeutiques pour les cancers colorectaux. Summary The mammalian intestine has one of the highest cellular turnover rates in the body. The complete intestinal epithelium is renewed in less than a week. It is divided into spatially distinct compartments in the form of finger-like projections (villi) and flask-shaped invaginations (crypts) that are dedicated to specific functions. Intestinal cells are constantly produced from a stem cell reservoir that gives rise to proliferating transient amplifying cells, which subsequently differentiate and home to their specific compartments before dying after having fulfilled their physiological function. In this thesis project, the physiological role of the Notch signalling cascade in the marine intestine was studied. Inducible tissue specific inactivation of Notch1, Notch2, Jagged1 and RBP-Jk genes was applied to assess their role in the maintenance of intestinal homeostasis and cell fate determination. The analysis unequivocally revealed that Notch1, Notch1 and Jagged1 combined as well as Notch2 are dispensable for intestinal homeostasis and lineage differentiation. However, deficiency of RBP-Jk as well as the simultaneous inactivation of both Notch1 and Notch2 receptors unveiled a striking phenotype. In these mice, a rapid and massive conversion of proliferative crypt cells into post-mitotic goblet cells was observed. These results identify the Notch pathway as a key player for the maintenance of the proliferative crypt compartment. A similar role was implicated for the Wnt cascade, which, however, was not affected in the different tissue specific Notch signalling deficient mice. Thus, the Wnt and Notch signalling pathways are essential for the self-renewal capacity of the intestinal epithelium. Furthermore, our results suggest a molecular mechanism for Notch signalling mediated control of cell cycle regulation within the crypt. The Notch cascade inhibits expression of the cyclin-dependent kinase inhibitor p27KIP1 and thereby maintains proliferation of the intestinal progenitor cells. In addition, the inactivation of RBP-Jk in adenomas developed by APCmin mice resulted in the differentiation of tumour cells into goblet cells. Finally, Notch deficiency affected differentiated Paneth cells, suggesting that Notch may play a role in the Paneth cell compartment. In summary, this work clearly demonstrates that undifferentiated, proliferative cells in intestinal crypts require the concerted activation of the RBP-Jk-mediated Notch signalling and the Wnt cascade. In addition, our preliminary results can be considered as a "proof-of-principle" for the use of γ-secretase inhibitors for therapeutic modalities for colorectal cancer.

Compositional data and Simpson's paradox

Simpson's paradox, also known as amalgamation or aggregation paradox, appears whendealing with proportions. Proportions are by construction parts of a whole, which canbe interpreted as compositions assuming they only carry relative information. TheAitchison inner product space structure of the simplex, the sample space of compositions, explains the appearance of the paradox, given that amalgamation is a nonlinearoperation within that structure. Here we propose to use balances, which are specificelements of this structure, to analyse situations where the paradox might appear. Withthe proposed approach we obtain that the centre of the tables analysed is a naturalway to compare them, which avoids by construction the possibility of a paradox.Key words: Aitchison geometry, geometric mean, orthogonal projection