Imaging Properties of MS Lesions Correlate with Attention Deficits in Early Multiple Sclerosis

Introduction: Cognitive impairment affects 40-65% of multiple sclerosis (MS) patients, often since early stages of the disease (relapsing remitting MS, RRMS). Frequently affected functions are memory, attention or executive abilities but the most sensitive measure of cognitive deficits in early MS is the information processing speed (Amato, 2008). MRI has been extensively exploited to investigate the substrate of cognitive dysfunction in MS but the underlying physiopathological mechanisms remain unclear. White matter lesion load, whole-brain atrophy and cortical lesions' number play a role but correlations are in some cases modest (Rovaris, 2006; Calabrese, 2009). In this study, we aimed at characterizing and correlating the T1 relaxation times of cortical and sub-cortical lesions with cognitive deficits detected by neuropsychological tests in a group of very early RR MS patients. Methods: Ten female patients with very early RRMS (age: 31.6 ±4.7y; disease duration: 3.8 ±1.9y; EDSS disability score: 1.8 ±0.4) and 10 age- and gender-matched healthy volunteers (mean age: 31.2 ±5.8y) were included in the study. All participants underwent the following neuropsychological tests: Rao's Brief Repeatable Battery of Neuropsychological tests (BRB-N), Stockings of Cambridge, Trail Making Test (TMT, part A and B), Boston Naming Test, Hooper Visual Organization Test and copy of the Rey-Osterrieth Complex Figure. Within 2 weeks from neuropsychological assessment, participants underwent brain MRI at 3T (Magnetom Trio a Tim System, Siemens, Germany) using a 32-channel head coil. The imaging protocol included 3D sequences with 1x1x1.2 mm3 resolution and 256x256x160 matrix, except for axial 2D-FLAIR: -DIR (T2-weighted, suppressing both WM and CSF; Pouwels, 2006) -MPRAGE (T1-weighted; Mugler, 1991) -MP2RAGE (T1-weighted with T1 maps; Marques, 2010) -FLAIR SPACE (only for patient 4-10, T2-weighted; Mugler, 2001) -2D Axial FLAIR (0.9x0.9x2.5 mm3, 256x256x44 matrix). Lesions were identified by one experienced neurologist and radiologist using all contrasts, manually contoured and assigned to regional locations (cortical or sub-cortical). Lesion number, volume and T1 relaxation time were calculated for lesions in each contrast and in a merged mask representing the union of the lesions from all contrasts. T1 relaxation times of lesions were normalized with the mean T1 value in corresponding control regions of the healthy subjects. Statistical analysis was performed using GraphPad InStat software. Cognitive scores were compared between patients and controls with paired t-tests; p values ≤ 0.05 were considered significant. Spearmann correlation tests were performed between the cognitive tests, which differed significantly between patients and controls, and lesions' i) number ii) volume iii) T1 relaxation time iv) disease duration and v) years of study. Results: Cortical and sub-cortical lesions count, T1 values and volume are reported in Table 1 (A and B). All early RRMS patients showed cortical lesions (CLs) and the majority consisted of CLs type I (lesions with a cortical component extending to the sub-cortical tissue). The rest of cortical lesions were characterized as type II (intra-cortical lesions). No type III/IV lesions (large sub-pial lesions) were detected. RRMS patients were slightly less educated (13.5±2.5y vs. 16.3±1.8y of study, p=0.02) than the controls. Signs of cortical dysfunction (i.e. impaired learning, language, visuo-spatial skills or gnosis) were rare in all patients. However, patients showed on average lower scores on measures of visual attention and information processing speed (TMT-part A: p=0.01; TMT-part B: p=0.006; PASAT-included in the BRB-N: p=0.04). The T1 relaxation values of CLs type I negatively correlated with the TMT-part A score (r=0.78, p<0.01). The correlations of TMT-part B score and PASAT score with T1 relaxation time of lesions as well and the correlation between TMT-part A, TMT-part B and PASAT score with lesions' i) number ii) volume iii) disease duration and iv) years of study did not reach significance. In order to preclude possible influences from partial volume effects on the T1 values, the correlation between lesion volume and T1 value of CLs type I was calculated; no correlation was found, suggesting that partial volume effects did not affect the statistics. Conclusions: The present pilot study reports for the first time the presence and the T1 characteristics at 3 T of cortical lesions in very early RRMS (< 6 y disease duration). It also shows that CLS type I represents the most frequent cortical lesion type in this cohort of RRMS patients. In addition, it reveals a negative correlation between the attentional test TMT-part A and the T1 properties of cortical lesions type I. In other words, lower attention deficits are concomitant with longer T1-relaxation time in cortical lesions. In respect to this last finding, it could be speculated that long relaxation time correspond to a certain degree of tissue loss that is enough to stimulate compensatory mechanisms. This hypothesis is in line with previous fMRI studies showing functional compensatory mechanisms to help maintaining normal or sub-normal attention performances in RR MS patients (Penner, 2003).

Long-Stay Activity Report 2004 - Supplementary Report

In 2004 the Annual Survey of Long Stay Units requested additional information on the types of beds in long stay units and how these beds are used and by whom. This additional information was sought to provide a more accurate picture of the activity in long stay units. Prior to 2004 the survey only requested information on number of respite beds. The analysis in the report referred to all beds and thus it was not possible to get a picture of the different types of activity carried out in the continuing care sector. In 2004 information on long stay and limited stay beds was sought. Read the report (PDF, 343kb) Read the original Report (PDF, 359kb)

Improving Quality of Life for Older People in Long-Stay Care Settings in Ireland

The quality of life of older people in all care settings is a primary concern of the National Council on Ageing and Older People (NCAOP); a concern echoed by the National Economic and Social Forum (NESF) in its recent report Care for Older Peoplein which it stated that â?~enhancing quality of life of older people in different settings should be a key policy priorityâ?T (NESF, 2005). Read the Report (PDF, 3.25mb) Read the Report on Conference Proceedings (PDF. 484kb)

New insights into the long-term evolutionary history of the avian MHC

SummaryGene duplication and neofunctidnalization are important processes in the evolution of phenotypic complexity. They account for important evolutionary novelties that confer ecological adaptation, such as the major histocompatibility complex (MHC), a multigene family with a central role in vertebrates' adaptive immune system. Multigene families, which evolved in large part through duplication, represent promising systems to study the still strongly depbated relative roles of neutral and adaptive processes in the evolution of phenotypic complexity. Detailed knowledge on ecological function and a well-characterized evolutionary history place the mammals' MHC amongst ideal study systems. However mammalian MHCs usually encompass several million base pairs and hold a large number of functional and non-functional duplicate genes, which makes their study complex. Avian MHCs on the other hand are usually way more compact, but the reconstruction of. their evolutionary history has proven notoriously difficult. However, no focused attempt has been undertaken so far to study the avian MHC evolutionary history in a broad phylogenetic context and using adequate gene regions.In the present PhD, we were able to make important contributions to the understanding of the long-term evolution of the avian MHC class II Β (MHCI1B). First, we isolated and characterized MHCIIB genes in barn owl (Tyto alba?, Strigiformes, Tytonidae), a species from an avian lineage in which MHC has not been studied so far. Our results revealed that with only two functional MHCIIB genes the MHC organization of barn owl may be similar to the 'minimal essential' MHC of chicken (Gallus gallus), indicating that simple MHC organization may be ancestral to birds. Taking advantage of the sequence information from barn owl, we studied the evolution of MHCIIB genes in 13 additional species of 'typical' owls (Strigiformes, Strigidae). Phylogenetic analyses revealed that according to their function, in owls the peptide-binding region (PBR) encoding exon 2 and the non-PBR encoding exon 3 evolve by different patterns. Exon 2 exhibited an evolutionary history of positive selection and recombination, while exon 3 traced duplication history and revealed two paralogs evolving divergently from each other in owls, and in a shorebird, the great snipe {Gallinago media). The results from exon 3 were the first ever from birds to demonstrate gene orthology in species that diverged tens of millions of years ago, and strongly questioned whether the taxa studied before provided an adequate picture of avian MHC evolution. In a follow-up study, we aimed at explaining a striking pattern revealed by phylogenetic trees analyzing the owl sequences along with MHCIIB sequences from other birds: One owl paralog (termed DAB1) grouped with sequences of passerines and falcons, while the other (DAB2) grouped with wildfowl, penguins and birds of prey. This could be explained by either a duplication event preceding the evolution of these bird orders, or by convergent evolution of similar sequences in a number of orders. With extensive phylogenetic analyses we were able to show, that indeed a duplication event preceeded the major avian radiation -100 my ago, and that following this duplication, the paralogs evolved under positive selection. Furthermore, we showed that the divergently evolving amino acid residues in the MHCIIB-encoded β-chain potentially interact with the MHCI I α-chain, and that molecular coevolution of the interacting residues may have been involved in the divergent evolution of the MHCIIB paralogs.The findings of this PhD are of particular interest to the understanding of the evolutionary history of the avian MHC and, by providing essential information on long-term gene history in the avian MHC, open promising perspectives for advances in the understanding of the evolution of multigene families in general, and for avian MHC organization in particular. Amongst others I discuss the importance of including protein structure in the phylogenetic study of multigene families, and the roles of ecological versus molecular selection pressures. I conclude by providing a population genomic perspective on avian MHC, which may serve as a basis for future research to investigate the relative roles of neutral processes involving effective population size effects and of adaptation in the evolution of avian MHC diversity and organization.RésuméLa duplication de gènes et leur néo-fonctionnalisation sont des processus importants dans l'évolution de la complexité phénotypique. Ils sont impliqués dans l'apparition d'importantes nouveautés évolutives favorisant l'adaptation écologique, comme c'est le cas pour le complexe majeur d'histocompatibilité long-terme du CMH aviaire classe II Β (CMH II Β). Nous avons isolé et caractérisé les gènes CMH I IB de la chouette effraie (Tyto alba; Strigiformes, Tytonidae), une espèce appartenant à une lignée aviaire dont le CMH n'avait pas été étudié jusqu'ici. Avec uniquement deux gènes CMHIIB fonctionnels, l'organisation CMH de la chouette effraie semble être comparable à celle "minimale" du poulet (Gallus gallus), ce qui suggère qu'une organisation simple du CMH pourrait être ancestrale chez les oiseaux. En se basant sur l'information obtenue pour cette espèce, nous avons ensuite étudié l'évolution des gènes CMHIIB chez 13 espèces de chouettes "typiques" (Strigiformes, Strigidae). Les analyses phylogénétiques ont révélé que chez les chouettes, selon leur fonction, l'exon 2 codant pour la 'peptide-binding region' (PBR) et l'exon 3 ne codant pas pour la région PBR évoluent de manière distincte. L'exon 2 montre une histoire évolutive de sélection positive et recombinaison, tandis que l'exon 3 retrace l'histoire de duplication et révèle deux paralogues évoluant de façon divergente chez les chouettes, ainsi que chez un limicole, la bécassine double (Gallinago media). Les résultats découlant de l'analyse de l'exon 3 ont montré pour la première fois chez les oiseaux une orthologie de gènes chez des espèces ayant divergé il y a des dizaines de millions d'années. Dans une deuxième étude, nous avons voulu expliquer le pattern surprenant révélé par les arbres phylogénétiques lorsque les séquences CMHIIB des chouettes sont analysées avec les séquences d'autres oiseaux: un paralogue de chouette (appelé DABI) forme un groupe avec les séquences de passereaux et faucons, tandis que l'autre (DAB2) se regroupe avec les gallo-ansériformes, les manchots et les rapaces diurnes. Ceci pourrait être expliqué soit par une duplication qui a précédé l'évolution de ces ordres aviaires soit par évolution convergente dans un certain nombre d'ordres. Grâce à des analyses phylogénétiques approfondies, nous avons pu montrer qu'un événement de duplication a effectivement précédé la radiation aviaire principale d'il y a environ 100 millions d'années, et qu'après cette duplication les paralogues ont évolué sous sélection positive. De plus, les résidus d'acides aminés évoluant de façon divergente dans la chaîne β codée par le CMHIIB interagissent potentiellement avec la chaîne α codée par le CMHII, et que la coévolution moléculaire de ces résidus pourrait être à la base de l'évolution divergente des paralogues CMHIIB.Dans cette thèse sont discutés entre autres l'importance d'inclure la structure des protéines dans l'étude phylogénétique des familles multigéniques, ainsi que les rôles respectifs des pressions sélectives écologique et moléculaire. La conclusion comporte une perspective sur la génomique des populations du CMH aviaire, qui pourrait servir de base pour de futures recherches sur les rôles relatifs joués par Îes processus neutres comprenant les effets de la taille efficace des populations et l'adaptation dans l'évolution de la diversité et l'organisation du MHC aviaire.

Long-Stay Activity Report 2005

Long-Stay Activity Report 2005 This report presents data collected through a survey of long-stay units in 2005. The aim of the survey is to provide statistics on the number of beds available for long-term care, how the beds are used and the types of patients who occupy these beds. In 2004, additional information on bed types was requested for the first time in order to provide a more accurate picture of activity within this sector. This report includes analysis on long-stay beds, limited-stay beds and all beds in each table. Click here to download PDF 867kb

End-of-Life Care for Older People in Acute and Long-Stay Care Settings in Ireland

The National Council on Ageing and Older People (NCAOP) and the Irish Hospice Foundation (IHF) are pleased to present this report, End-of-Life Care for Older People in Acute and Long-Stay Care Settings in Ireland. The report details the results of research that focuses, for the first time in Ireland, on the quality oflife and quality of care at the end-of-life for older people in various care settings including acute hospitals, public extended care units, private nursing homes, voluntary nursing homes and welfare homes. The report provides a new model for care at the end-of-life which goes beyond specialist palliative care provision to embrace a compassionate approach that supports older people who are living with, or dying from, progressive, chronic and life-threatening conditions, and attends to all their needs: physical, psychological,social and spiritual. Download document here

Long Stay Activity Report for 2006

Long Stay Activity Report for 2006 This report presents data collected through a survey of long-stay units in 2006. The aim of the survey is to provide statistics on the number of beds available for long-term care, how the beds are used and the types of patients who occupy these beds. In order to present the data this report has been divided into a number of sections. This introductory section examines how data was collected and analysed and gives a summary of the results. Click here to download PDF 2mb

Report of the Interdepartmental Working Group on Long Term Care, 2006

Report of the Interdepartmental Working Group on Long Term Care, 2006 This report was finalised by the working group at the end of 2005 and submitted to Government in January 2006. While the reportâ?Ts proposals were not formally endorsed by Government, its analysis and recommendations have informed subsequent decisions, including the Fair Deal policy on Long-Term Nursing Home Care.The principles underpinning the report formed the basis for discussions about long term care with the Social Partners prior to the new national programme negotiations leading to a clear vision articulated in Towards 2016 on a number of priority actions to support older people to participate in society in a full and meaningful way. Click here to download PDF 693kb

Laboratory diagnosis of Schistosomiasis in areas of low transmission: a review of a line of research

After 57 years of successful control of schistosomiasis in Venezuela, the prevalence and intensity of infection have declined. Approximately 80% of the individuals eliminate less than 100 eggs/g of stools, therefore morbidity is mild and the majority are asymptomatic. The sensitivity of Kato-Katz decreases to approximately 60%. Available serological methods for the detection of circulating antigens only reach a 70% of sensitivity. Tests based on the detection of antibodies by immunoenzymatic assays have been improved. The circumoval precipitine test has shown a high sensitivity (97%), specificity (100%), and correlation with oviposition, being considered the best confirmatory diagnostic test. Additionally to the classical immunoenzymatic assays, the development of the alkaline phosphatase immunoassay, allowed to reach a 100% specificity with an 89% sensitivity. Recently, we have developed a modified ELISA in which the soluble egg antigen is treated with sodium metaperiodate (SMP-ELISA) in order to eliminate the glycosilated epitopes responsible for the false positive reactions. The specificity and sensitivity reaches 97% and 99%, respectively. Synthetic peptides from the excretory-secretory enzymes, cathepsin B (Sm31) legumain (Sm32) and cathepsin D (Sm45), have been synthesized. The combination of two peptides derived from the Sm31 have been evaluated, reaching a sensitivity of 96% when analyzed independently and with a 100% specificity. Antibodies raised in rabbits against peptides derived from the Sm31 and Sm32 are currently evaluated in two different antigen-capture-based assays. The development of a simple, cheap and reliable test that correlates with parasite activity is a major goal.

Value for Money Report - The Efficiency and Effectiveness of Long-Stay Residential Care for Adults within the Mental Health Services

Value for Money Report – The Efficiency and Effectiveness of Long-Stay Residential Care for Adults within the Mental Health Services Executive Summary and Contents PDF 164kb Chapters 1 and 2 – Introduction and Service Objectives PDF 504kb Chapter 3 plus annexes – Service Effectiveness and Efficiency PDF 3.7mb Chapter 4 – Service Resources PDF 2.4mb Chapters 5, 6 and 7 – Future Funding and Alternative Approaches, Key Performance Indicators, Conclusions and Recommendations PDF 2.4mb Appendices 1 to 6

Response evaluation in third- and fourth-line treatment of GIST: the role of PET

Background: Response evaluation in gastrointestinal stromal tumors is difficult. Computed tomography and size-based assessments have been found inadequate to draw prognostic conclusions in patients treated with tyrosine kinase inhibitors (TKI). Density criteria (CHOI) have recently been shown to better define prognostic subsets of patients evaluated with CT. Still, positron emission tomography (PET) might be better at identifying responders with good outcome early, as shown for first and recently second-line treatment in GIST (Prior et al.; J Clin Oncol 2009). We wanted to evaluate the role of PET in third- and fourth-line TKI treatment of GIST. Methods: We retrospectively reviewed patients with GIST who had received third- or fourth-line treatment with TKI and had undergone PET for response evaluation. Patient needed to have a baseline and at least one subsequent PET. Results of the first "early" PET after treatment start have been used throughout this analysis and EORTC PET Study Group criteria applied. Results: Twelve treatment courses were evaluable, seven with Nilotinib in third- and five with Sorafenib in fourth-line treatment, in 8 patients, median age 60 y (range 36−78 y), who had all failed prior Imatinib and Sunitinib treatment due to disease progession. Baseline and follow-up PET were performed within a median of 34 days (range 9−84 days). Median progression-free survival (PFS) was 262 days in patients responding to PET versus 76 days in patients with stable or progressing disease (p = 0.15). Conclusions: This small series suggests that PET retains its value for outcome prediction in third- and fourth-line TKI treatment of GIST. This could be of particular clinical value in these vulnerable patients with large tumour masses. Early PET may help in stopping ineffective, but toxic therapy and help switching to a more effective therapy. PET should be evaluated further in this patient population.

Long Stay Activity Report for 2008

Long Stay Activity Report for 2008 Click here to download PDF 2.7mb

Long Stay Activity Report for 2007

Long Stay Activity Report for 2007 Click here to download PDF 2.5mb

Long Stay Activity Report for 2010

Long Stay Activity Report for 2010 Click here to download PDF 1.42MB

Long Stay Activity Report for 2009

Long Stay Activity Report for 2009 Click here to download PDF 2.19MB