Immune responses to JC virus in patients with multiple sclerosis treated with natalizumab: a cross-sectional and longitudinal study.

BACKGROUND: Natalizumab is used to prevent relapses and progression of disability in patients with multiple sclerosis but has been associated with progressive multifocal leukoencephalopathy (PML). We aimed to better understand the associations between JC virus, which causes PML, and natalizumab treatment. METHODS: We prospectively assessed patients with multiple sclerosis who started treatment with natalizumab. Blood and urine samples were tested for the presence of JC virus DNA with quantitative real-time PCR before treatment and at regular intervals after treatment onset for up to 18 months. At the same timepoints, by use of proliferation and enzyme-linked immunospot assays, the cellular immune responses against JC virus, Epstein-Barr virus, cytomegalovirus, myelin oligodendrocyte glycoprotein, and myelin oligodendrocyte basic protein (MOBP) were assessed. Humoral immune response specific to JC virus was assessed with an enzyme immunoassay. The same experiments were done on blood samples from patients with multiple sclerosis before and 10 months after the start of interferon beta treatment. FINDINGS: We assessed 24 patients with multiple sclerosis who received natalizumab and 16 who received interferon beta. In patients treated with natalizumab, JC virus DNA was not detected in the blood at any timepoint. However, JC virus DNA was present in the urine of six patients and in most of these patients the concentrations of JC virus DNA were stable over time. Compared with pretreatment values, the cellular immune response was increased to cytomegalovirus at 6 months, to JC virus at 1, 9, and 12 months, and to Epstein-Barr virus and MOBP at 12 months. Humoral responses remained stable. There were no increases in cellular immune responses specific to the viruses or myelin proteins in the 16 patients treated with interferon beta. INTERPRETATION: Natalizumab increases cellular immune responses specific to viruses and myelin proteins in the peripheral blood after 1 year, without evidence of viral reactivation. FUNDING: Swiss National Foundation, Swiss Society for Multiple Sclerosis, and Biogen Dompé.

Portraying innovation in the public service of Brazil: Frameworks, systematization and characterization

ABSTRACT Innovation is essential for improving organizational performance in both the private and public sectors. This article describes and analyzes the 323 innovation experiences of the Brazilian federal public service that received prizes during the 16 annual competitions (from 1995 to 2012) of the Award for Innovation in Federal Public Management held by the Brazilian National School of Public Administration (ENAP). It is a qualitative and quantitative study in which were employed as categories for analysis the four types of innovation defined in the Copenhagen Manual: product, process, organizational and communication. The survey results allow us to affirm that there is innovation in the public sector, in spite of the skepticism of some researchers and the incipient state of theoretical research on the subject. It was possible to observe that organizational innovation was the one with the highest number of award- -winning experience, followed respectively by process, communication and product innovation, with citizen services and improvement of work processes being the main highlights. The results showed that, although the high incidence of innovation occurs at the national level, a significant number of innovations also occur at the local level, probably because many organizations of the federal government have their actions spread only at this level of government. Concerning the innovative area, health and education predominate, with almost 33% of initiatives, which can be explained by capillarity of these areas and the fact that both maintain a strong interaction with the user. The contributions of this work include the use of theoretical model of innovation analysis in the public sector in Brazil still upcoming, and the systematization of knowledge in empirical basis for this innovation. In this sense, it also contributes to the development of the theory with the presentation of evidence that the characteristics, determinants and consequences of innovation in the public sector differ not only from innovation in the industry, but also from innovation in services in the private sector.

Road Equipment Procurement and Utilization Study, October 2002

Final report of road equipment procurement and utilization study.

Tetrasomy 8 in a patient with acute nonlymphocytic leukemia: a metaphase and interphase study with fluorescence in situ hybridization.

Tetrasomy 8 constitutes a relatively rare recurring chromosome defect in myeloid disorders. The patient reported here, a 71-year-old man, presented with tetrasomy 8 as the sole chromosome abnormality associated with an acute nonlymphocytic leukemia of the M2 type. He failed to respond to chemotherapy and died one year after diagnosis. Following conventional cytogenetics and fluorescence in situ hybridization (FISH) with a centromeric probe specific for chromosome 8, tetrasomy 8 was detected in 61% of the metaphases analyzed and trisomy 8 in 39%. FISH analysis of interphase nuclei confirmed the existence of tetrasomic (35%) and trisomic cells (56%) and revealed a number of cells with two chromosomes 8 (8%). This normal population may represent lymphocytes or myeloid cells that escaped conventional analysis due to their inability to divide or to the small number of metaphases available. The relatively higher proportion of tetrasomic cells in metaphase compared with interphase may be attributed to a proliferative advantage of tetrasomic cells in vitro or to the longer duration of their cell cycle. The simultaneous presence of trisomic and tetrasomic cells confirms the hypothesis of a clonal relationship between trisomy 8 and tetrasomy 8. Our case brings further evidence to the specificity of tetrasomy 8 to myeloid disorders and to the association of this chromosome abnormality with a relatively poor prognosis. However, new patients must be studied to further delineate this cytogenetic entity.

Composition of fingermark residue: a qualitative and quantitative review

This article describes the composition of fingermark residue as being a complex system with numerous compounds coming from different sources and evolving over time from the initial composition (corresponding to the composition right after deposition) to the aged composition (corresponding to the evolution of the initial composition over time). This complex system will additionally vary due to effects of numerous influence factors grouped in five different classes: the donor characteristics, the deposition conditions, the substrate nature, the environmental conditions and the applied enhancement techniques. The initial and aged compositions as well as the influence factors are thus considered in this article to provide a qualitative and quantitative review of all compounds identified in fingermark residue up to now. The analytical techniques used to obtain these data are also enumerated. This review highlights the fact that despite the numerous analytical processes that have already been proposed and tested to elucidate fingermark composition, advanced knowledge is still missing. Thus, there is a real need to conduct future research on the composition of fingermark residue, focusing particularly on quantitative measurements, aging kinetics and effects of influence factors. The results of future research are particularly important for advances in fingermark enhancement and dating technique developments.

Experimental and computational study on the synthesis and characterization of self-assembling meso/macroporous materials in highly concentrated emulsions

Report for the scientific sojourn carried out at Massachusetts General Hospital Cancer Center-Harvard Medical School, Estats Units, from 2010 to 2011. The project aims to study the aggregation behavior of amphiphilic molecules in the continuous phase of highly concentrated emulsions, which can be used as templates for the synthesis of meso/macroporous materials. At this stage of the project, we have investigated the self-assembly of diblock and triblock surfactants under the effect of a confined geometry being surrounded by the droplets of the dispersed phase. These droplets limit the growth of the aggregates, deeply modify their orientation and hence alter their spatial arrangement as compared to the self-assembly taking place far enough from any boundary surface, that is in the bulk. By performing Monte Carlo simulations, we have showed that the interface between the dispersed and continuous phases as well as its shape has a significant impact on the structural order of the resulting aggregates and hence on the potential applications of highly concentrated emulsions as reaction media, drug delivery systems, or templates for meso/macroporous materials. Due to the combined effect of symmetry breaking and morphological frustration, very intriguing structures, such as square columnar liquid crystals, twisted X-shaped aggregates, and helical phases of cylindrical aggregates, never observed in the bulk for the same model surfactant, have been found. The presence of other more conventional structures, such as micelles and cubic and hexagonal liquid crystals, formed at low and high amphiphilic concentrations, respectively, further enhance the interest on this already rich aggregation behavior.

Influence of physico-chemical material characteristics on staphylococcal biofilm formation--a qualitative and quantitative in vitro analysis of five different calcium phosphate bone grafts.

Various compositions of synthetic calcium phosphates (CaP) have been proposed and their use has considerably increased over the past decades. Besides differences in physico-chemical properties, resorption and osseointegration, artificial CaP bone graft might differ in their resistance against biofilm formation. We investigated standardised cylinders of 5 different CaP bone grafts (cyclOS, chronOS (both β-TCP (tricalcium phosphate)), dicalcium phosphate (DCP), calcium-deficient hydroxyapatite (CDHA) and α-TCP). Various physico-chemical characterisations e.g., geometrical density, porosity, and specific surface area were investigated. Biofilm formation was carried out in tryptic soy broth (TSB) and human serum (SE) using Staphylococcus aureus (ATCC 29213) and S. epidermidis RP62A (ATCC 35984). The amount of biofilm was analysed by an established protocol using sonication and microcalorimetry. Physico-chemical characterisation showed marked differences concerning macro- and micropore size, specific surface area and porosity accessible to bacteria between the 5 scaffolds. Biofilm formation was found on all scaffolds and was comparable for α-TCP, chronOS, CDHA and DCP at corresponding time points when the scaffolds were incubated with the same germ and/or growth media, but much lower for cyclOS. This is peculiar because cyclOS had an intermediate porosity, mean pore size, specific surface area, and porosity accessible to bacteria. Our results suggest that biofilm formation is not influenced by a single physico-chemical parameter alone but is a multi-step process influenced by several factors in parallel. Transfer from in vitro data to clinical situations is difficult; thus, advocating the use of cyclOS scaffolds over the four other CaP bone grafts in clinical situations with a high risk of infection cannot be clearly supported based on our data.

Total knee arthroplasty - a clinical and numerical study of the micromovements of the tibial implant

Introduction The importance of the micromovements in the mechanism of aseptic loosening is clinically difficult to evaluate. To complete the analysis of a series of total knee arthroplasties (TKA), we used a tridimensional numerical model to study the micromovements of the tibial implant.Material and Methods Fifty one patients (with 57 cemented Porous Coated Anatomic TKAs) were reviewed (mean follow-up 4.5 year). Radiolucency at the tibial bone-cement interface was sought on the AP radiographs and divided in 7 areas. The distribution of the radiolucency was then correlated with the axis of the lower limb as measured on the orthoradiograms.The tridimensional numerical model is based on the finite element method. It allowed the measurement of the cemented prosthetic tibial implant's displacements and the microvements generated at bone-ciment interface. A total load (2000 Newton) was applied at first vertically and asymetrically on the tibial plateau, thereby simulating an axial deviation of the lower limbs. The vector's posterior inclination then permitted the addition of a tangential component to the axial load. This type of effort is generated by complex biomechanical phenomena such as knee flexion.Results 81 per cent of the 57 knees had a radiolucent line of at least 1 mm, at one or more of the tibial cement-epiphysis jonctional areas. The distribution of these lucent lines showed that they came out more frequently at the periphery of the implant. The lucent lines appeared most often under the unloaded margin of the tibial plateau, when axial deviation of lower limbs was present.Numerical simulations showed that asymetrical loading on the tibial plateau induced a subsidence of the loaded margin (0-100 microns) and lifting off at the opposite border (0-70 microns). The postero-anterior tangential component induced an anterior displacement of the tibial implant (160-220 microns), and horizontal micromovements with non homogenous distribution at the bone-ciment interface (28-54 microns).Discussion Comparison of clinical and numerical results showed a relation between the development of radiolucent lines and the unloading of the tibial implant's margin. The deleterious effect of lower limbs' axial deviation is thereby proven. The irregular distribution of lucent lines under the tibial plateau was similar of the micromovements' repartition at the bone-cement interface when tangential forces were present. A causative relation between the two phenomenaes could not however be established.Numerical simulation is a truly useful method of study; it permits to calculate micromovements which are relative, non homogenous and of very low amplitude. However, comparative clinical studies remain as essential to ensure the credibility of results.

Geochemical and geothermal study of springs in the Ossola-Simplon Region

Geological, hydrogeological and geochemical surveys were carried out in the Piedilago area (Ossola-Simplon region) in order to investigate the geothermal resources present in this area. Following these surface exploration efforts an exploratory geothermal well of 248 m was drilled in 1991. It discharges a thermal water with temperatures up to 43 degrees C and calcium (sodium) sulphate composition with a TDS close to 1350 mg/l. Chemical geothermometers suggest a reservoir temperature close to 45 degrees C indicating that the well virtually produces the pure uncooled thermal water. The Piedilago ex-ample is here considered as the departure point to establish both general criteria for further geothermal investigations in young mountains chains and taking into consideration all the available data on geology and fluid geochemistry of thermal systems in the Ossola-Simplon region, to constrain a geothermal model for the Lower Pennine Zone.

Organization of healthcare and assistance to the elderly indigenous population: synergies and particularities of the professional context

This study aimed to describe the effects of the organization of primary healthcare on the assistance provided to the elderly Kaingang population, according to the perception of health professionals that work in this area. It is a qualitative and descriptive study, supported by ethnography methodological references, and was conducted with ten healthcare professionals that work in Faxinal, an indigenous territory in the state of Paraná, in Brazil. Data was collected from November 2010 to February 2012 through participant observation and interviews. The results revealed that health professionals strive to meet the health needs of the elderly Kaingang people; however, there are negative effects that hinder the professional care, especially limited human resources, lack of training and material resources, heavy workload and high turnover rates. This study highlights the need to improve work conditions in order to provide better healthcare.

Qualitative and Hierarchical Analysis of Protective Factors against Illicit Use of Doping Substances in Athletes Calling a National Anti-Doping Phone-Help Service

Evidence of a sport-specific hierarchy of protective factors against doping would thus be a powerful aid in adapting information and prevention campaigns to target the characteristics of specific athlete groups, and especially those athletes most vulnerable for doping control. The contents of phone calls to a free and anonymous national anti-doping service called 'ecoute dopage' were analysed (192 bodybuilders, 124 cyclists and 44 footballers). The results showed that the protective factors that emerged from analysis could be categorised into two groups. The first comprised 'Health concerns', 'Respect for the law' and 'Doping controls from the environment' and the second comprised 'Doubts about the effectiveness of illicit products, 'Thinking skills' and 'Doubts about doctors'. The ranking of the factors for the cyclists differed from that of the other athletes. The ordering of factors was 1) respect for the law, 2) doping controls from the environment, 3) health concerns 4) doubts about doctors, and 5) doubts about the effectiveness illicit products. The results are analysed in terms of the ranking in each athlete group and the consequences on the athletes' experience and relationship to doping. Specific prevention campaigns are proposed to limit doping behaviour in general and for each sport.

Acute effects of transmyocardial laser revascularization on left-ventricular function: an haemodynamic and echocardiographic study.

While the lesions produced by transmyocardial laser revascularisation (TMLR) induce scar formation, it is important to determine whether this procedure can be deleterious for the left-ventricular function, which is already impaired by the underlying ischaemic process in some patients. Ten channels were drilled in the left lateral wall of the hearts of ten pigs (mean weight, 61 +/- 8.2kg) with a Holmium:YAG laser. Haemodynamic measurements and echocardiographic assessment of left-ventricular function were performed before the TMLR procedure, 5 and 30 min after, and lastly after 5 min of pacing at a rate increased by 30% of the baseline value. Echocardiographic assessment was in the short axis at the level of the laser channels, and included left-ventricular ejection fraction and segmental wall motility of the lasered area (scale 0-3:0 = normal 1 = hypokinesia, 2 = akinesia, 3 = dyskinesia). Values at 5 and 30 min were compared with baseline values; the difference was considered significant if p < 0.05. Haemodynamical values were stable throughout all the procedures. The ejection fraction showed a slight but significant decrease 5 min after the creation of the channels (60.4 +/- 6.8% vs 54 +/- 7.6%, p=0.02) and recovered at 30min. The segmental motility score of the involved areas increased to 1 after 5 min in five animals, and came back to 0 at 30 min except in one animal. Even with pacing no segmental dysfunction occurred. The reversibility of the segmental hypokinesia induced by TMLR, as well as the absence of pace-induced dysfunction 30 min after the procedure strongly suggest the inocuity of TMLR in this experimental set-up.

Phenetic, biogeographical, and evolutionary study ofOrnithogalum subg.Heliocharmos (Hyacinthaceae) in the western Mediterranean basin

A macromorphological study is made on taxa of the genusOrnithogalum subg.Heliocharmos in North Africa, Spain, and France. The results obtained are consistent with data from cytogenetics, reproductive biology and strategies of reproduction. They allow the retention of two species:O. algeriense and O. umbellatum. A biogeographical and phylogenetic interpretation of the subgenus is proposed for the western Mediterranean. Theoretical views on phenetics are discussed.

Relationship of aerobic fitness and motor skills with memory and attention in preschoolers (Ballabeina): A cross-sectional and longitudinal study.

Background: The debate about a possible relationship between aerobic fitness and motor skills with cognitive development in children has recently re-emerged, because of the decrease in children's aerobic fitness and the concomitant pressure of schools to enhance cognitive performance. As the literature in young children is scarce, we examined the cross-sectional and longitudinal relationship of aerobic fitness and motor skills with spatial working memory and attention in preschool children.Methods: Data from 245 ethnically diverse preschool children (mean age: 5.2 (0.6) years, girls: 49.4%) analyzed at baseline and 9 months later. Assessments included aerobic fitness (20 m shuttle run) and motor skills with agility (obstacle course) and dynamic balance (balance beam). Cognitive parameters included spatial working memory (IDS) and attention (KHV-VK). All analyses were adjusted for age, sex, BMI, migration status, parental education, native language and linguistic region. Longitudinal analyses were additionally adjusted for the respective baseline value.Results: In the cross-sectional analysis, aerobic fitness was associated with better attention (r = 0.16, p = 0.03). A shorter time in the agility test was independently associated with a better performance both in working memory (r = -0.17, p = 0.01) and in attention (r = -0.20, p = 0.01). In the longitudinal analyses, baseline aerobic fitness was independently related to improvements in attention (r = 0.16, p = 0.03), while baseline dynamic balance was associated with improvements in working memory (r = 0.15, p = 0.04).Conclusions: In young children, higher baseline aerobic fitness and motor skills were related to a better spatial working memory and/or attention at baseline, and to some extent also to their future improvements over the following 9 months.