Gross Hemoglobinuria and Oliguria are Common Transient Complications of Sclerotherapy for Venous Malformations: Review of 475 Procedures.

Estudi retrospectiu per analitzar la incidència, factors de risc i tractament de la hemoglobinuria macroscòpica i oliguria després del tractament de malformacions venoses amb escleroteràpia. Un total de 475 procediments es van realitzar en 131 malalts usant etanol, sulfat tetradecil sòdic o ambdos. Hemoglobinuria temporal es va donar després del 34% de procediments i el 57% d’aquests es van asociar amb oliguria temporal. Aquest risc augmenta amb el increment de dosis. La resolució de la hemoglobinuria i oliguria va ser satisfactòria en tots els malalts. El risc d’hemoglobinuria augmenta a les malformacions que afecten les extremitats inferiors i a les de localitzacions mútiples.

Quantitative integration of geophysical and hydraulic data : from the local towards the regional scale range

Des progrès significatifs ont été réalisés dans le domaine de l'intégration quantitative des données géophysique et hydrologique l'échelle locale. Cependant, l'extension à de plus grandes échelles des approches correspondantes constitue encore un défi majeur. Il est néanmoins extrêmement important de relever ce défi pour développer des modèles fiables de flux des eaux souterraines et de transport de contaminant. Pour résoudre ce problème, j'ai développé une technique d'intégration des données hydrogéophysiques basée sur une procédure bayésienne de simulation séquentielle en deux étapes. Cette procédure vise des problèmes à plus grande échelle. L'objectif est de simuler la distribution d'un paramètre hydraulique cible à partir, d'une part, de mesures d'un paramètre géophysique pertinent qui couvrent l'espace de manière exhaustive, mais avec une faible résolution (spatiale) et, d'autre part, de mesures locales de très haute résolution des mêmes paramètres géophysique et hydraulique. Pour cela, mon algorithme lie dans un premier temps les données géophysiques de faible et de haute résolution à travers une procédure de réduction déchelle. Les données géophysiques régionales réduites sont ensuite reliées au champ du paramètre hydraulique à haute résolution. J'illustre d'abord l'application de cette nouvelle approche dintégration des données à une base de données synthétiques réaliste. Celle-ci est constituée de mesures de conductivité hydraulique et électrique de haute résolution réalisées dans les mêmes forages ainsi que destimations des conductivités électriques obtenues à partir de mesures de tomographic de résistivité électrique (ERT) sur l'ensemble de l'espace. Ces dernières mesures ont une faible résolution spatiale. La viabilité globale de cette méthode est testée en effectuant les simulations de flux et de transport au travers du modèle original du champ de conductivité hydraulique ainsi que du modèle simulé. Les simulations sont alors comparées. Les résultats obtenus indiquent que la procédure dintégration des données proposée permet d'obtenir des estimations de la conductivité en adéquation avec la structure à grande échelle ainsi que des predictions fiables des caractéristiques de transports sur des distances de moyenne à grande échelle. Les résultats correspondant au scénario de terrain indiquent que l'approche d'intégration des données nouvellement mise au point est capable d'appréhender correctement les hétérogénéitées à petite échelle aussi bien que les tendances à gande échelle du champ hydraulique prévalent. Les résultats montrent également une flexibilté remarquable et une robustesse de cette nouvelle approche dintégration des données. De ce fait, elle est susceptible d'être appliquée à un large éventail de données géophysiques et hydrologiques, à toutes les gammes déchelles. Dans la deuxième partie de ma thèse, j'évalue en détail la viabilité du réechantillonnage geostatique séquentiel comme mécanisme de proposition pour les méthodes Markov Chain Monte Carlo (MCMC) appliquées à des probmes inverses géophysiques et hydrologiques de grande dimension . L'objectif est de permettre une quantification plus précise et plus réaliste des incertitudes associées aux modèles obtenus. En considérant une série dexemples de tomographic radar puits à puits, j'étudie deux classes de stratégies de rééchantillonnage spatial en considérant leur habilité à générer efficacement et précisément des réalisations de la distribution postérieure bayésienne. Les résultats obtenus montrent que, malgré sa popularité, le réechantillonnage séquentiel est plutôt inefficace à générer des échantillons postérieurs indépendants pour des études de cas synthétiques réalistes, notamment pour le cas assez communs et importants où il existe de fortes corrélations spatiales entre le modèle et les paramètres. Pour résoudre ce problème, j'ai développé un nouvelle approche de perturbation basée sur une déformation progressive. Cette approche est flexible en ce qui concerne le nombre de paramètres du modèle et lintensité de la perturbation. Par rapport au rééchantillonage séquentiel, cette nouvelle approche s'avère être très efficace pour diminuer le nombre requis d'itérations pour générer des échantillons indépendants à partir de la distribution postérieure bayésienne. - Significant progress has been made with regard to the quantitative integration of geophysical and hydrological data at the local scale. However, extending corresponding approaches beyond the local scale still represents a major challenge, yet is critically important for the development of reliable groundwater flow and contaminant transport models. To address this issue, I have developed a hydrogeophysical data integration technique based on a two-step Bayesian sequential simulation procedure that is specifically targeted towards larger-scale problems. The objective is to simulate the distribution of a target hydraulic parameter based on spatially exhaustive, but poorly resolved, measurements of a pertinent geophysical parameter and locally highly resolved, but spatially sparse, measurements of the considered geophysical and hydraulic parameters. To this end, my algorithm links the low- and high-resolution geophysical data via a downscaling procedure before relating the downscaled regional-scale geophysical data to the high-resolution hydraulic parameter field. I first illustrate the application of this novel data integration approach to a realistic synthetic database consisting of collocated high-resolution borehole measurements of the hydraulic and electrical conductivities and spatially exhaustive, low-resolution electrical conductivity estimates obtained from electrical resistivity tomography (ERT). The overall viability of this method is tested and verified by performing and comparing flow and transport simulations through the original and simulated hydraulic conductivity fields. The corresponding results indicate that the proposed data integration procedure does indeed allow for obtaining faithful estimates of the larger-scale hydraulic conductivity structure and reliable predictions of the transport characteristics over medium- to regional-scale distances. The approach is then applied to a corresponding field scenario consisting of collocated high- resolution measurements of the electrical conductivity, as measured using a cone penetrometer testing (CPT) system, and the hydraulic conductivity, as estimated from electromagnetic flowmeter and slug test measurements, in combination with spatially exhaustive low-resolution electrical conductivity estimates obtained from surface-based electrical resistivity tomography (ERT). The corresponding results indicate that the newly developed data integration approach is indeed capable of adequately capturing both the small-scale heterogeneity as well as the larger-scale trend of the prevailing hydraulic conductivity field. The results also indicate that this novel data integration approach is remarkably flexible and robust and hence can be expected to be applicable to a wide range of geophysical and hydrological data at all scale ranges. In the second part of my thesis, I evaluate in detail the viability of sequential geostatistical resampling as a proposal mechanism for Markov Chain Monte Carlo (MCMC) methods applied to high-dimensional geophysical and hydrological inverse problems in order to allow for a more accurate and realistic quantification of the uncertainty associated with the thus inferred models. Focusing on a series of pertinent crosshole georadar tomographic examples, I investigated two classes of geostatistical resampling strategies with regard to their ability to efficiently and accurately generate independent realizations from the Bayesian posterior distribution. The corresponding results indicate that, despite its popularity, sequential resampling is rather inefficient at drawing independent posterior samples for realistic synthetic case studies, notably for the practically common and important scenario of pronounced spatial correlation between model parameters. To address this issue, I have developed a new gradual-deformation-based perturbation approach, which is flexible with regard to the number of model parameters as well as the perturbation strength. Compared to sequential resampling, this newly proposed approach was proven to be highly effective in decreasing the number of iterations required for drawing independent samples from the Bayesian posterior distribution.

Deciphering the unusual HLA-A2/Melan-A/MART-1-specific TCR repertoire in humans.

The Melan-A/MART-1(26-35) antigenic peptide is one of the best studied human tumor-associated antigens. It is expressed in healthy melanocytes and malignant melanoma and is recognized by CD8(+) T cells in the context of the MHC class I molecule HLA-A*0201. While an unusually large repertoire of CD8(+) T cells specific for this antigen has been documented, the reasons for its generation have remained elusive. In this issue of the European Journal of Immunology, Pinto et al. [Eur. J. Immunol. 2014. 44: 2811-2821] uncover one important mechanism by comparing the thymic expression of the Melan-A gene to that in the melanocyte lineage. This study shows that medullary thymic epithelial cells (mTECs) dominantly express a truncated Melan-A transcript, the product of misinitiation of transcription. Consequently, the protein product in mTECs lacks the immunodominant epitope spanning residues 26-35, thus precluding central tolerance to this antigen. In contrast, melanocytes and melanoma tumor cells express almost exclusively the full-length Melan-A transcript, thus providing the target antigen for efficient recognition by HLA-A2-restricted CD8(+) T cells. The frequency of these alternative gene transcription modes may be more common than previously appreciated and may represent an important factor modulating the efficiency of central tolerance induction in the thymus.

Assessing multiple sclerosis activity: is the in vitro production of tumor necrosis factor-alpha, interleukins 2, 6, 4, and 10, and immunoglobulin G of value?

Tumor necrosis factor (TNF) alpha, interleukins (IL) 2, 4, 6, and 10, and IgG oligoclonal bands (IgG OB) in vitro production was assessed, after whole-blood stimulation with lipopolysaccharide or concanavalin A, in 61 patients presenting with relapsing-remitting, relapsing-progressive, or chronic progressive multiple sclerosis. Multiple sclerosis patients were receiving no treatment or azathioprine (AZA), cyclosporin, cyclophosphamide, subcutaneous interferon (IFN) beta 1 a, or corticosteroids (CST). Statistical correlations significantly showed that: (a) AZA lowers TNF-alpha (P = 0.002) and increases IL-4 production (P = 0.0024), and IFN-beta 1 a increases TNF-alpha and decreases IL-4 levels; (b) CST has a negative effect on TNF-alpha, IL-6, and IL-4 synthesis; and (c) AZA, IFN-beta 1 a, and CST diminish IgG OB synthesis (P = 0.001). Although our study of the dynamics of TNF-alpha, IL-2, IL-4, IL-6, and IL-10 in vitro production generally found no statistically significant correlations (partly explained by the limited number of values in the various groups), IL-6 was shown to drop during the periods surrounding relapse (P = 0.05) in the absence of treatment, while TNF-alpha (P = 0.04) and IL-6 (P < 0.05) dropped before exacerbation in the presence of AZA. In vitro production of TNF-alpha was closely and positively correlated with that of IL-6, independently of clinical features. The enhanced production of IL-10 detected before or at relapse with AZA and IFN-beta 1 a (trends) may interfere with initiation of the immune reaction and with the development of new CNS lesions. Some discrepancies with previously published results stress the difficulties in studying the state of stimulation of different populations of leukocytes by using a variety of in vitro stimuli and in establishing a correlation between mRNA studies and the amount of final or active protein produced.

Immunodéficience commune variable: ce qu'il faut savoir [Common variable immune deficiency: what you need to know].

Common variable immune deficiency is the most frequent primary immune deficiency, characterized mainly by a disorder of B lymphocytes differentiation and a deficit in immunoglobulins. The clinical manifestations include recurrent infections, non-infectious lung and digestive involvements, autoimmune diseases, and an increased susceptibility to cancers. Recent breakthroughs have been made in the understanding of some genetic mechanisms of the disease. Replacement therapy with intravenous immunoglobulins remains the treatment of choice, which allows significant improvement in the survival and quality of life. However progress should be made in the understanding of the pathophysiology and in the early detection of this disease, since a delay in the diagnosis may have harmful consequences in terms of morbidity and mortality.

Audit of the Irish health system for value for money

In April 2000, Deloitte & Touche in conjunction with the York Health Economics Consortium were chosen by The Department of Health & Children to carry out an examination of the health services over the past ten years Download the Report here

Avian erythrocytes have functional mitochondria, opening novel perspectives for birds as animal models in the study of ageing.

BACKGROUND: In contrast to mammalian erythrocytes, which have lost their nucleus and mitochondria during maturation, the erythrocytes of almost all other vertebrate species are nucleated throughout their lifespan. Little research has been done however to test for the presence and functionality of mitochondria in these cells, especially for birds. Here, we investigated those two points in erythrocytes of one common avian model: the zebra finch (Taeniopygia guttata). RESULTS: Transmission electron microscopy showed the presence of mitochondria in erythrocytes of this small passerine bird, especially after removal of haemoglobin interferences. High-resolution respirometry revealed increased or decreased rates of oxygen consumption by erythrocytes in response to the addition of respiratory chain substrates or inhibitors, respectively. Fluorometric assays confirmed the production of mitochondrial superoxide by avian erythrocytes. Interestingly, measurements of plasmatic oxidative markers indicated lower oxidative stress in blood of the zebra finch compared to a size-matched mammalian model, the mouse. CONCLUSIONS: Altogether, those findings demonstrate that avian erythrocytes possess functional mitochondria in terms of respiratory activities and reactive oxygen species (ROS) production. Interestingly, since blood oxidative stress was lower for our avian model compared to a size-matched mammalian, our results also challenge the idea that mitochondrial ROS production could have been one actor leading to this loss during the course of evolution. Opportunities to assess mitochondrial functioning in avian erythrocytes open new perspectives in the use of birds as models for longitudinal studies of ageing via lifelong blood sampling of the same subjects.

Seroepidemiological markers of enterically transmitted viral hepatitis A and E in individuals living in a community located in the North Area of Rio de Janeiro, RJ, Brazil

We investigated the seroprevalence of hepatitis A virus (HAV) and hepatitis E virus (HEV) infection in subjects living in the community of Manguinhos, Rio de Janeiro, Brazil, and assisted at the Health Unit of Escola Nacional de Saúde Pública, Fundação Oswaldo Cruz. After formal consent, individuals were submitted to an interview using a standardized questionnaire. Anti-HAV and anti-HEV antibodies were detected by ELISA. Statistical analysis was carried out using the Epi-Info 6.04b software, to investigate possible associations between serological markers and risk factors. Results were regarded as significant when p value < 0.05. Although a high prevalence of anti-HAV was observed (87%), almost 50% of subjects under the age of 10 were susceptible to HAV infection, an unexpected rate in endemic areas. This fact could be attributed to improvements in environmental sanitation, occurring in this area in the last years. The increasing proportion of susceptible people may result in outbreaks of HAV infection, since the virus still circulates in this area, as verified by the detection of anti-HAV IgM in some individuals. No statistical association was met between HAV infection and the risk factors here assessed. The anti-HEV IgG prevalence found in this population was 2.4%, consistent with the one found in non-endemic areas.

Cadmium distribution in soils covering Jurassic oolitic limestone with high Cd contents in the Swiss Jura

Oolitic carbonates belonging to the Hauptrogenstein Formation of Bajocian (Middle Jurassic) age have been shown to be anomalously enriched in cadmium (Cd) throughout the Jura Mountains. Soils associated with this type of rock substratum may be naturally polluted with regards to Cd. At Schleifenberg (Canton Basel Land, Switzerland) the Hauptrogenstein Formation is almost entirely exposed along a trail on its SW flank. Cadmium concentrations were systematically measured throughout this formation and Cd enrichments in rocks are shown to occur to a maximum content of 4.9 mg kg(-1). We investigated associated soils, which cover the entire outcrop, and show that they have been formed through the weathering of the underlying bedrock and through the uptake of colluvial limestone fragments from the same and older formations. Cadmium contents in the soils reach a maximum value of 2.0 mg kg(-1), thereby exceeding the official Swiss indicative guideline value for soils fixed at 0.8 mg.kg(-1). Mineralogical analyses on the soils and associated bedrock suggest that no allochthonous component related to aeolian transport is present. Sequential extractions applied to selected soil samples show that about half of the Cd resides in the carbonate fraction coming from the fractured parent-rock, while the Cd released from the weathered carbonates is associated either with organic matter (over 10%) or with Fe and Mn-oxihydroxides (approximately 30%). No exchangeable Cd phase was found and this, together with the buffer capacity of this calcareous soil, suggests that the amount of mobile Cd is quite negligible in this soil, which also greatly reduces the amount of bioavailable

High prevalence anti-Trypanosoma cruzi antibodies, among blood donors in the State of Puebla, a non-endemic area of Mexico

Blood transfusion is the second most common transmission route of Chagas disease in many Latin American countries. In Mexico, the prevalence of Chagas disease and impact of transfusion of Trypanosoma cruzi-contaminated blood is not clear. We determined the seropositivity to T. cruzi in a representative random sample, of 2,140 blood donors (1,423 men and 647 women, aged 19-65 years), from a non-endemic state of almost 5 millions of inhabitants by the indirect hemagglutination (IHA) and enzyme linked immunosorbent assay (ELISA) tests using one autochthonous antigen from T. cruzi parasites, which were genetically characterized like TBAR/ME/1997/RyC-V1 (T. cruzi I) isolated from a Triatoma barberi specimen collected in the same locality. The seropositivity was up to 8.5% and 9% with IHA and ELISA tests, respectively, and up to 7.7% using both tests in common. We found high seroprevalence in a non-endemic area of Mexico, comparable to endemic countries where the disease occurs, e.g. Brazil (0.7%), Bolivia (13.7%) and Argentina (3.5%). The highest values observed in samples from urban areas, associated to continuous rural emigration and the absence of control in blood donors, suggest unsuspected high risk of transmission of T. cruzi, higher than those reported for infections by blood e.g. hepatitis (0.1%) and AIDS (0.1%) in the same region.

Troubles cognitifs séquellaires de la rupture d'anévrysmes de l'artère communicante antérieure et de l'artère cérébrale antérieure. Etude rétrospective de 56 cas [Cognitive sequelae following rupture of aneurysms of the anterior communicating artery and the anterior cerebral artery. Retrospective study of 56 cases].

The neuropsychological records of 56 patients operated for clipping were studied. Almost every patient remained autonomous and without invalidating motor defect. The present study was aimed at specifying the type and frequency of neuropsychological sequelae and, to a lesser extent, the role of various pathophysiological factors. A main concern was to examine to what extent and at what post-operative interval the neuropsychological assessment can predict the intellectual and socioprofessional outcome of each individual patient. The neuropsychological assessment performed beyond the acute phase showed evidence of intellectual sequelae in about two thirds of the patients. Only one case of permanent anterograde amnesia was observed, probably due to unavoidable inclusion of a hypothalamic artery in the clip during surgery. Transient anterograde amnesia and confabulations were occasionally observed, generally for less than three weeks. A common finding was impaired performance on memory and/or executive tests. In a minority of patients, language disorders, visuoperceptive and visuoconstructive disabilities were found, probably in relation with hemodynamic changes at distance from the aneurysm. Global impairment of intellectual function was not uncommon in the acute post-operative phase but it evolved in most cases towards a more selective impairment, for instance restricted to executive and memory functions, in the chronic phase. The neuropsychological investigation carried out 4 to 15 weeks post-operatively provided satisfactory information about possible long-lasting intellectual disturbances and professional resumption. In particular, persistent global intellectual impairment, persistent amnesia and confabulations 4-15 weeks post-operative were associated with cessation of professional activity; executive and memory impairment, behavioral disturbances such as those encountered in patients with frontal lobe damage were associated with a decreased probability of full-time employment. Pre- and post-operative angiography were not good predictors of long-term cognitive outcome: normal angiography was not necessarily followed by normal neuropsychological outcome, conversely abnormal angiography could be found together with normal neuropsychological outcome. By contrast, there was a relationship between left-lateralised abnormalities on post-operative angiography and occurrence of language disorders; similarly, there was a relationship between side of craniotomy and type of deficits, that is language disorders versus visuoperceptive-visuoconstructive impairments.

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

The tangible common denominator of substance use disorders: a reply to commentaries to Rehm et al. (2013a).

In response to our suggestion to define substance use disorders via 'heavy use over time', theoretical and conceptual issues, measurement problems and implications for stigma and clinical practice were raised. With respect to theoretical and conceptual issues, no other criterion has been shown, which would improve the definition. Moreover, heavy use over time is shown to be highly correlated with number of criteria in current DSM-5. Measurement of heavy use over time is simple and while there will be some underestimation or misrepresentation of actual levels in clinical practice, this is not different from the status quo and measurement of current criteria. As regards to stigma, research has shown that a truly dimensional concept can help reduce stigma. In conclusion, 'heavy use over time' as a tangible common denominator should be seriously considered as definition for substance use disorder.

Value for Money and Policy Review of Disability Services in Ireland

This Review is an evaluation of the efficiency and effectiveness of the HSE-funded statutory and non-statutory disability services in Ireland. It was conducted by the Department of Health and the HSE under the auspices of the Governmentâ?Ts programme of Value for Money Reviews for 2009-2011. It makes a range of recommendations about how these services should be structured. www.dohc.ie/press/releases/2012/20120720.html Click here to download PDF 3.7mb Value for Money and Policy Review of the Disability Services Programme – Recommendation PDF 205kb Value for Money and Policy Review of the Disability Services Programme – Questions & Answers PDF 44kb Value for Money and Policy Review of the Disability Services Programme – Questions & Answers PDF 151kb  

Value for Money and Policy Review of Disability Services in Ireland - National Implementation Framework

The National Implementation Framework describes how the recommendations from the Value for Money (VFM) and Policy Review of the Disability Services Programme will be translated into concrete actions. It assigns responsibilities for those actions, and specifies timelines for their completion. It also identifies priorities and key performance indicators. The Framework describes how these reforms can be achieved in a planned, timely and cost effective manner. Click here to download (PDF 876KB)