High diagnostic efficiency of IgM-ELISA with the use of multiple antigen peptides (MAP1) from T. gondii ESA (SAG-1, GRA-1 and GRA-7), in acute toxoplasmosis

The main serological marker for the diagnosis of recent toxoplasmosis is the specific IgM antibody, along with IgG antibodies of low avidity. However, in some patients these antibodies may persist long after the acute/recent phase, contributing to misdiagnosis in suspected cases of toxoplasmosis. In the present study, the diagnostic efficiency of ELISA was evaluated, with the use of peptides derived from T. gondii ESA antigens, named SAG-1, GRA-1 and GRA-7. In the assay referred to, we studied each of these peptides individually, as well as in four different combinations, as Multiple Antigen Peptides (MAP), aiming to establish a reliable profile for the acute/recent toxoplasmosis with only one patient serum sample. The diagnostic performance of the assay using MAP1, with the combination of SAG-1, GRA-1 and GRA-7 peptides, demonstrated better discrimination of the acute/recent phase from non acute/recent phase of toxoplasmosis. Our results show that IgM antibodies to MAP1 may be useful as a serological marker, enhancing the diagnostic efficiency of the assay for acute/recent phase of toxoplasmosis.

Design of assemblies based on polymer-coated quantum dots and organic dye

During last years, photophysical properties of complexes of semiconductor quantum dots (QDs) with organic dyes have attracted increasing interest. The development of different assemblies based on QDs and organic dyes allows to increase the range of QDs applications, which include imaging, biological sensing and electronic devices.1 Some studies demonstrate energy transfer between QDs and organic dye in assemblies.2 However, for electronic devices purposes, a polymeric matrix is required to enhance QDs photostability. Thus, in order to attach the QDs to the polymer surface it is necessary to chemically modify the polymer to induce electronic charges and stabilize the QDs in the polymer. The present work aims to investigate the design of assemblies based on polymer-coated QDs and an integrated acceptor organic dye. Polymethylmethacrylate (PMMA) and polycarbonate (PC) were used as polymeric matrices, and nile red as acceptor. Additionally, a PMMA matrix modified with 2-mercaptoethylamine is used to improve the attachment between both the donor (QDs) and the acceptor (nile red), as well as to induce a covalent bond between the modified PMMA and the QDs. An enhancement of the energy transfer efficiency by using the modified PMMA is expected and the resulting assembly can be applied for energy harvesting.

Are cognitive interventions for multiple sclerosis effective and feasible?

Purpose: Fifty percent of patients with Multiple Sclerosis (MS) are estimated to have cognitive impairments leading to considerable decline in productivity and quality of life. Cognitive intervention has been considered to complement pharmacological treatments. However, a lack of agreement concerning the efficacy of cognitive interventions in MS still exists. A systematic review and meta-analysis was conducted to assess the effects of cognitive interventions in MS. Methods: To overcome limitations of previous meta-analyses, several databases were searched only for Randomized Clinical Trials (RCTs) with low risk of bias. Results: Five studies (total of 139 participants) met our eligibility criteria. Although good completion and adherence rates were evident, we found no evidence of intervention effects on cognition or mood in post-intervention or follow-up assessments. Conclusions: This is the first meta-analysis assessing the effects of cognitive intervention in MS including only RCTs with comparable conditions. Research regarding efficacy, cost-effectiveness and feasibility is still in its infancy. Caution is advised when interpreting these results due to the small number of RCTs meeting the inclusion criteria. Considering the costs of disease, good completion and adherence rates of this approach, further research is warranted. Recommendations concerning improved research practices in the field are presented as well.

Cognitive functioning and efficacy of cognitive intervention in Multiple Sclerosis

Tese de Doutoramento em Psicologia Clínica / Psicologia

Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium

Type 2 diabetes (T2D) has been suggested to be a risk factor for multiple myeloma (MM), but the relationship between the two traits is still not well understood. The aims of this study were to evaluate whether 58 genome-wide-association-studies (GWAS)-identified common variants for T2D influence the risk of developing MM and to determine whether predictive models built with these variants might help to predict the disease risk. We conducted a case–control study including 1420 MM patients and 1858 controls ascertained through the International Multiple Myeloma (IMMEnSE) consortium. Subjects carrying the KCNQ1rs2237892T allele or the CDKN2A-2Brs2383208G/G, IGF1rs35767T/T and MADDrs7944584T/T genotypes had a significantly increased risk of MM (odds ratio (OR)=1.32–2.13) whereas those carrying the KCNJ11rs5215C, KCNJ11rs5219T and THADArs7578597C alleles or the FTOrs8050136A/A and LTArs1041981C/C genotypes showed a significantly decreased risk of developing the disease (OR=0.76–0.85). Interestingly, a prediction model including those T2D-related variants associated with the risk of MM showed a significantly improved discriminatory ability to predict the disease when compared to a model without genetic information (area under the curve (AUC)=0.645 vs AUC=0.629; P=4.05×10-06). A gender-stratified analysis also revealed a significant gender effect modification for ADAM30rs2641348 and NOTCH2rs10923931 variants (Pinteraction=0.001 and 0.0004, respectively). Men carrying the ADAM30rs2641348C and NOTCH2rs10923931T alleles had a significantly decreased risk of MM whereas an opposite but not significant effect was observed in women (ORM=0.71 and ORM=0.66 vs ORW=1.22 and ORW=1.15, respectively). These results suggest that TD2-related variants may influence the risk of developing MM and their genotyping might help to improve MM risk prediction models.

Peroxisomal beta-oxidation--a metabolic pathway with multiple functions.

Fatty acid degradation in most organisms occurs primarily via the beta-oxidation cycle. In mammals, beta-oxidation occurs in both mitochondria and peroxisomes, whereas plants and most fungi harbor the beta-oxidation cycle only in the peroxisomes. Although several of the enzymes participating in this pathway in both organelles are similar, some distinct physiological roles have been uncovered. Recent advances in the structural elucidation of numerous mammalian and yeast enzymes involved in beta-oxidation have shed light on the basis of the substrate specificity for several of them. Of particular interest is the structural organization and function of the type 1 and 2 multifunctional enzyme (MFE-1 and MFE-2), two enzymes evolutionarily distant yet catalyzing the same overall enzymatic reactions but via opposite stereochemistry. New data on the physiological roles of the various enzymes participating in beta-oxidation have been gathered through the analysis of knockout mutants in plants, yeast and animals, as well as by the use of polyhydroxyalkanoate synthesis from beta-oxidation intermediates as a tool to study carbon flux through the pathway. In plants, both forward and reverse genetics performed on the model plant Arabidopsis thaliana have revealed novel roles for beta-oxidation in the germination process that is independent of the generation of carbohydrates for growth, as well as in embryo and flower development, and the generation of the phytohormone indole-3-acetic acid and the signal molecule jasmonic acid.

Simulations of parasitic and intrinsic capacitances related to Multiple-Gate-Field-Effect Transistor architectures

Report for the scientific sojourn carried out at the Université Catholique de Louvain, Belgium, from March until June 2007. In the first part, the impact of important geometrical parameters such as source and drain thickness, fin spacing, spacer width, etc. on the parasitic fringing capacitance component of multiple-gate field-effect transistors (MuGFET) is deeply analyzed using finite element simulations. Several architectures such as single gate, FinFETs (double gate), triple-gate represented by Pi-gate MOSFETs are simulated and compared in terms of channel and fringing capacitances for the same occupied die area. Simulations highlight the great impact of diminishing the spacing between fins for MuGFETs and the trade-off between the reduction of parasitic source and drain resistances and the increase of fringing capacitances when Selective Epitaxial Growth (SEG) technology is introduced. The impact of these technological solutions on the transistor cut-off frequencies is also discussed. The second part deals with the study of the effect of the volume inversion (VI) on the capacitances of undoped Double-Gate (DG) MOSFETs. For that purpose, we present simulation results for the capacitances of undoped DG MOSFETs using an explicit and analytical compact model. It monstrates that the transition from volume inversion regime to dual gate behaviour is well simulated. The model shows an accurate dependence on the silicon layer thickness,consistent withtwo dimensional numerical simulations, for both thin and thick silicon films. Whereas the current drive and transconductance are enhanced in volume inversion regime, our results show thatintrinsic capacitances present higher values as well, which may limit the high speed (delay time) behaviour of DG MOSFETs under volume inversion regime.

Can Early Intervention Policies Improve Well-being? Evidence from a randomized controlled trial

Many authors have proposed incorporating measures of well-being into evaluations of public policy. Yet few evaluations use experimental design or examine multiple aspects of well-being, thus the causal impact of public policies on well-being is largely unknown. In this paper we examine the effect of an intensive early intervention program on maternal well-being in a targeted disadvantaged community. Using a randomized controlled trial design we estimate and compare treatment effects on global well-being using measures of life satisfaction, experienced well-being using both the Day Reconstruction Method (DRM) and a measure of mood yesterday, and also a standardized measure of parenting stress. The intervention has no significant impact on negative measures of well-being, such as experienced negative affect as measured by the DRM and global measures of well-being such as life satisfaction or a global measure of parenting stress. Significant treatment effects are observed on experienced measures of positive affect using the DRM, and a measure of mood yesterday. The DRM treatment effects are primarily concentrated during times spent without the target child which may reflect the increased effort and burden associated with additional parental investment. Our findings suggest that a maternal-focused intervention may produce meaningful improvements in experienced well-being. Incorporating measures of experienced affect may thus alter cost-benefit calculations for public policies.

Income stratification and the measurement of interdistributional inequality between multiple groups

This paper proposes a new class of stratification indices that measure interdistributional inequality between multiple groups. The class is based on a conceptualisation of stratification as a process that results in a hierarchical ordering of groups and therefore seeks to capture not only the extent to which groups form well-defined strata in the income distribution but also the scale of the resultant differences in income standards between them, where these two factors play the same role as identification and alienation respectively in the measurement of polarisation. The properties of the class as a whole are investigated as well as those of selected members of it: zeroth and first power indices may be interpreted as measuring the overall incidence and depth of stratification respectively, while higher power indices members are directly sensitive to the severity of stratification between groups. An illustrative application provides an empirical analysis of global income stratification by regions in 1993.

Teaching foreign languages through translation: considering multiple intelligences

Aquest treball de recerca tracta de la relació existent entre pedagogia, traducció, llengües estrangeres i intel•ligències múltiples. El debat sobre si la traducció és una eina útil a la classe de llengües estrangeres és un tema actual sobre el qual molts investigadors encara indaguen. Estudis recents, però, han demostrat que qualsevol tasca de traducció -en la qual s’hi poden incloure treballs amb les diferents habilitats- és profitosa si la considerem un mitjà, no una finalitat en ella mateixa. Evidentment, l’ús de la traducció dins l’aula és avantatjosa, però també hem de tenir presents certs desavantatges d’aquesta aplicació. Un possible desavantatge podria ser la creença que, al principi, molta gent té referent a l’equivalència, paraula per paraula, d’una llengua vers una altra. Però després de presentar vàries tasques de traducció als estudiants, aquests poden arribar a controlar, fins i tot, les traduccions inconscients i poden assolir un cert nivell de precisió i flexibilitat que val la pena mencionar. Però l’avantatge principal és que s’enfronten a una activitat molt estesa dins la societat actual que combina dues llengües, la llengua materna i la llengua objecte d’estudi, per exemple. De tot això en podem deduir que utilitzar la llengua materna a la classe no s’ha de considerar un crim, com fins ara, sinó una virtut, evidentment si és emprada correctament. En aquest treball de recerca s’hi pot trobar una síntesi tant de les principals teories d’adquisició i aprenentatge de llengües com de les teories de traducció. A la pregunta de si les teories, tant de traducció com de llengües estrangeres, s’haurien d’ensenyar implícita o explícitament, es pot inferir que segons el nivell d’estudis on estiguin els aprenents els convindrà aprendre les teories explícitament o les aprendran, de totes maneres, implícitament. Com que qualsevol grup d’estudiants és heterogeni -és a dir que cada individu té un ritme i un nivell d’aprenentatge concret i sobretot cadascú té diferents estils de percepció (visual, auditiu, gustatiu, olfactiu, de moviment) i per tant diferents intel•ligències-, els professors ho han de tenir en compte a l’hora de planificar qualsevol programa d’actuació vers els alumnes. Per tant, podem concloure que les tasques o projectes de traducció poden ajudar als alumnes a aprendre millor, més eficaçment i a aconseguir un aprenentatge més significatiu.

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).

Multiple non-ossifying fibromas as a cause of pathological femoral fracture in Jaffe-Campanacci syndrome.

BACKGROUND: Jaffe-Campanacci is a rare syndrome characterised by the association of café-au-lait spots, axillary freckles, multiple non-ossifying fibromas of the long bones and jaw, as well as some features of type 1 neurofibromatosis. There are less than 30 reported cases, and a genetic profile has not yet been determined. Furthermore, it has not been clarified whether it is a subtype of type 1 neurofibromatosis or a separate syndrome. The risk of pathological fracture is over 50%, due to substantial cortical thinning of the weight-bearing bones. CASE PRESENTATION: A 17-year-old female patient, known for type 1 neurofibromatosis, presented with a low-energy distal femoral fracture due to disseminated large non-ossifying fibromas. Investigations revealed all of the distinctive signs of Jaffe-Campanacci syndrome. Both her distal femurs and proximal tibias exhibited multiple non-ossifying fibromas. The fracture was treated by open reduction and internal plate fixation. Some of the bony lesions were biopsied to confirm the diagnosis. The fracture healed eventless, as did the lesions biopsied or involved in the fracture. The other ones healed after curettage and bone grafting performed at the time of plate removal. CONCLUSION: Jaffe-Campanacci is a rare syndrome having unclear interactions with type 1 neurofibromatosis, which still needs to be characterised genetically. It is associated with a high risk of pathological fracture, due to the presence of multiple large non-ossifying fibromas of the long bones, with an expected normal healing time. Curettage and bone grafting promote healing of the lesions and should be considered to prevent pathological fracture. We agree with other authors that all patients with newly-diagnosed type 1 neurofibromatosis should undergo an osseous screening to detect disseminated non-ossifying fibromas, and evaluate the inherent risk of pathological fracture.

Multiple imputations applied to the DREAM3 phosphoproteomics challenge: a winning strategy.

DREAM is an initiative that allows researchers to assess how well their methods or approaches can describe and predict networks of interacting molecules [1]. Each year, recently acquired datasets are released to predictors ahead of publication. Researchers typically have about three months to predict the masked data or network of interactions, using any predictive method. Predictions are assessed prior to an annual conference where the best predictions are unveiled and discussed. Here we present the strategy we used to make a winning prediction for the DREAM3 phosphoproteomics challenge. We used Amelia II, a multiple imputation software method developed by Gary King, James Honaker and Matthew Blackwell[2] in the context of social sciences to predict the 476 out of 4624 measurements that had been masked for the challenge. To chose the best possible multiple imputation parameters to apply for the challenge, we evaluated how transforming the data and varying the imputation parameters affected the ability to predict additionally masked data. We discuss the accuracy of our findings and show that multiple imputations applied to this dataset is a powerful method to accurately estimate the missing data. We postulate that multiple imputations methods might become an integral part of experimental design as a mean to achieve cost savings in experimental design or to increase the quantity of samples that could be handled for a given cost.

Multiple adenosine 3',5'-cyclic [corrected] monophosphate response element DNA-binding proteins generated by gene diversification and alternative exon splicing.

The protein sequence deduced from the open reading frame of a human placental cDNA encoding a cAMP-responsive enhancer (CRE)-binding protein (CREB-327) has structural features characteristic of several other transcriptional transactivator proteins including jun, fos, C/EBP, myc, and CRE-BP1. Results of Southwestern analysis of nuclear extracts from several different cell lines show that there are multiple CRE-binding proteins, which vary in size in cell lines derived from different tissues and animal species. To examine the molecular diversity of CREB-327 and related proteins at the nucleic acid level, we used labeled cDNAs from human placenta that encode two different CRE-binding proteins (CREB-327 and CRE-BP1) to probe Northern and Southern blots. Both probes hybridized to multiple fragments on Southern blots of genomic DNA from various species. Alternatively, when a human placental c-jun probe was hybridized to the same blot, a single fragment was detected in most cases, consistent with the intronless nature of the human c-jun gene. The CREB-327 probe hybridized to multiple mRNAs, derived from human placenta, ranging in size from 2-9 kilobases. In contrast, the CRE-BP1 probe identified a single 4-kilobase mRNA. Sequence analyses of several overlapping human genomic cosmid clones containing CREB-327 sequences in conjunction with polymerase chain reaction indicates that the CREB-327/341 cDNAs are composed of at least eight or nine exons, and analyses of human placental cDNAs provide direct evidence for at least one alternatively spliced exon. Analyses of mouse/hamster-human hybridoma DNAs by Southern blotting and polymerase chain reaction localizes the CREB-327/341 gene to human chromosome 2. The results indicate that there is a dichotomy of CREB-like proteins, those that are related by overall structure and DNA-binding specificity as well as those that are related by close similarities of primary sequences.

Cluster analysis of behavioural and event-related potentials during a contingent negative variation paradigm in remitting-relapsing and benign forms of multiple sclerosis

Background: Event-related potentials (ERPs) may be used as a highly sensitive way of detecting subtle degrees of cognitive dysfunction. On the other hand, impairment of cognitive skills is increasingly recognised as a hallmark of patients suffering from multiple sclerosis (MS). We sought to determine the psychophysiological pattern of information processing among MS patients with the relapsing-remitting form of the disease and low physical disability considered as two subtypes: 'typical relapsing-remitting' (RRMS) and 'benign MS' (BMS). Furthermore, we subjected our data to a cluster analysis to determine whether MS patients and healthy controls could be differentiated in terms of their psychophysiological profile.Methods: We investigated MS patients with RRMS and BMS subtypes using event-related potentials (ERPs) acquired in the context of a Posner visual-spatial cueing paradigm. Specifically, our study aimed to assess ERP brain activity in response preparation (contingent negative variation -CNV) and stimuli processing in MS patients. Latency and amplitude of different ERP components (P1, eN1, N1, P2, N2, P3 and late negativity -LN) as well as behavioural responses (reaction time -RT; correct responses -CRs; and number of errors) were analyzed and then subjected to cluster analysis. Results: Both MS groups showed delayed behavioural responses and enhanced latency for long-latency ERP components (P2, N2, P3) as well as relatively preserved ERP amplitude, but BMS patients obtained more important performance deficits (lower CRs and higher RTs) and abnormalities related to the latency (N1, P3) and amplitude of ERPs (eCNV, eN1, LN). However, RRMS patients also demonstrated abnormally high amplitudes related to the preparation performance period of CNV (cCNV) and post-processing phase (LN). Cluster analyses revealed that RRMS patients appear to make up a relatively homogeneous group with moderate deficits mainly related to ERP latencies, whereas BMS patients appear to make up a rather more heterogeneous group with more severe information processing and attentional deficits. Conclusions: Our findings are suggestive of a slowing of information processing for MS patients that may be a consequence of demyelination and axonal degeneration, which also seems to occur in MS patients that show little or no progression in the physical severity of the disease over time.