Correlating liposomal adjuvant characteristics to in-vivo cell-mediated immunity using a novel Mycobacterium tuberculosis fusion protein:a multivariate analysis study

Objective In this study, we have used a chemometrics-based method to correlate key liposomal adjuvant attributes with in-vivo immune responses based on multivariate analysis. Methods The liposomal adjuvant composed of the cationic lipid dimethyldioctadecylammonium bromide (DDA) and trehalose 6,6-dibehenate (TDB) was modified with 1,2-distearoyl-sn-glycero-3-phosphocholine at a range of mol% ratios, and the main liposomal characteristics (liposome size and zeta potential) was measured along with their immunological performance as an adjuvant for the novel, postexposure fusion tuberculosis vaccine, Ag85B-ESAT-6-Rv2660c (H56 vaccine). Partial least square regression analysis was applied to correlate and cluster liposomal adjuvants particle characteristics with in-vivo derived immunological performances (IgG, IgG1, IgG2b, spleen proliferation, IL-2, IL-5, IL-6, IL-10, IFN-γ). Key findings While a range of factors varied in the formulations, decreasing the 1,2-distearoyl-sn-glycero-3-phosphocholine content (and subsequent zeta potential) together built the strongest variables in the model. Enhanced DDA and TDB content (and subsequent zeta potential) stimulated a response skewed towards a cell mediated immunity, with the model identifying correlations with IFN-γ, IL-2 and IL-6. Conclusion This study demonstrates the application of chemometrics-based correlations and clustering, which can inform liposomal adjuvant design.

Temporal analysis of land use and transportation investments with geographic information system

Land use and transportation interaction has been a research topic for several decades. There have been efforts to identify impacts of transportation on land use from several different perspectives. One focus has been the role of transportation improvements in encouraging new land developments or relocation of activities due to improved accessibility. The impacts studied have included property values and increased development. Another focus has been on the changes in travel behavior due to better mobility and accessibility. Most studies to date have been conducted in metropolitan level, thus unable to account for interactions spatially and temporally at smaller geographic scales. ^ In this study, a framework for studying the temporal interactions between transportation and land use was proposed and applied to three selected corridor areas in Miami-Dade County, Florida. The framework consists of two parts: one is developing of temporal data and the other is applying time series analysis to this temporal data to identify their dynamic interactions. Temporal GIS databases were constructed and used to compile building permit data and transportation improvement projects. Two types of time series analysis approaches were utilized: univariate models and multivariate models. Time series analysis is designed to describe the dynamic consequences of time series by developing models and forecasting the future of the system based on historical trends. Model estimation results from the selected corridors were then compared. ^ It was found that the time series models predicted residential development better than commercial development. It was also found that results from three study corridors varied in terms of the magnitude of impacts, length of lags, significance of the variables, and the model structure. Long-run effect or cumulated impact of transportation improvement on land developments was also measured with time series techniques. The study offered evidence that congestion negatively impacted development and transportation investments encouraged land development. ^

A comparative analysis of self-determined evaluations of work performance and support needs by adults with mental retardation in supported work and in sheltered workshop environments

The purpose of this study was to determine if there was a difference in the self-determined evaluations of work performance and support needs by adults with mental retardation in supported employment and in sheltered workshop environments. The instrument, Job Observation and Behavior Scale: Opportunity for Self-Determination (JOBS: OSD; Brady, Rosenberg, & Frain, 2006), was administered to 38 adults with mental retardation from sheltered workshops and 32 adults with mental retardation from supported employment environments. Cross-tabulations with Chi-square tests and independent samples t-tests were conducted to evaluate differences between the two groups, sheltered workshop and supported work. Two Multivariate Analyses of Variance (MANOVAs) were conducted to determine the effect of work environment on Quality of Performance (QP) and Types of Support (TS) test scores and their subscales. ^ This study found that there were significant differences between the groups on the QP Behavior and Job Duties subscales. The sheltered workshop group perceived themselves as performing significantly better on job duties than the supported work group. Conversely, the supported work group perceived themselves to have better behavior than the sheltered workshop group. However, there were no significant differences between groups in their perception of support needs for the three subscales. ^ The findings imply that work environment affects the self-determined evaluations of work performance by adults with mental retardation. Recommendations for further study include (a) detailing the characteristics of supported work and sheltered workshops that support and/or discourage self-determined behaviors, (b) exploring the behavior of adults with mental retardation in sheltered workshops and supported work environments, and (c) analysis of the support needs for and understanding of them by adults with mental retardation in sheltered workshops and in supported work environments. ^

``This is your brain on drugs'': The public policy of anti -drug programming. An exploratory analysis of media and other sources of drug information for adolescents

In the 1980s, government agencies sought to utilize research on drug use prevention to design media campaigns. Enlisting the assistance of the national media, several campaigns were designed and initiated to bring anti-drug use messages to adolescents in the form of public service advertising. This research explores the sources of information selected by adolescents in grades 7 through 12 and how the selection of media and other sources of information relate to drug use behavior and attitudes and perceptions related to risk/harm and disapproval of friends' drug-using activities.^ Data collected from 1989 to 1992 in the Miami Coalition School Survey provided a random selection of secondary school studies. The responses of these students were analyzed using multivariate statistical techniques.^ Although many of the students selected media as the source for most of their information on the effects of drugs on the people who use them, the selection of media was found to be positively related to alcohol use and negatively related to marijuana use. The selection of friends, brothers, or sisters was a statistically significant source for adolescents who smoke cigarettes, use alcohol or marijuana.^ The results indicate that the anti-drug use messages received by students may be canceled out by media messages perceived to advocate substance use and that a more persuasive source of information for adolescents may be friends and siblings. As federal reports suggest that the economic costs of drug abuse will reach an estimated $150 billion by 1997 if current trends continue, prevention policy that addresses the glamorization of substance use remains a national priority. Additionally, programs that advocate prevention within the peer cluster must be supported, as peers are an influential source for both inspiring and possibly preventing drug use behavior. ^

The effect of reciprocal mapping on high-risk sixth-grade students' social studies achievement

Reading deficits in students in Grades 4 to 12 are evident in American schools. Informational text is particularly difficult for students. This quasi-experimental study (N=138) investigated sixth-grade students' achievement in social studies using the Reciprocal Mapping instructional routine, compared to sixth-grade students' achievement taught with a traditional approach. The Reciprocal Mapping instructional routine incorporated explicit instruction in text structure using graphic organizers. Students created their own graphic organizers and used them to write about social studies content. The comparison group used a traditional approach, students' reading the textbook and answering questions. Students for this study included sixth-graders in the seven sixth-grade classrooms in two public schools in a small, rural south Florida school district. A focus of this study was to determine the helpfulness of the intervention for at-risk readers. To determine students considered to be at-risk, the researcher used data from the reading portion of the Florida Comprehensive Assessment Test (FCAT), 2011-2012, that considers Level 1 and 2 as at-risk readers. The quasi-experimental study used a pretest-posttest control group design, with students assigned to treatment groups by class. Two teachers at the two rural sites were trained on the Reciprocal Mapping instructional routine and taught students in both the experimental and control groups for an equivalent amount of time over a 5-week period. Results of the 3 x 2 factorial ANCOVA found a significant positive difference favoring the experimental group's social studies achievement as compared to that of the comparison group as measured by the pre/post unit test from the social studies series (McGraw-Hill, 2013), when controlling for initial differences in students' reading FCAT scores. Interactions for high-risk struggling readers were investigated using the significance level p < .05. Due to no significant interaction the main effects of treatment were interpreted. The pretest was used as a covariate and the multivariate analysis was found to be significant. Therefore, analysis of covariance was run on each of the dependent variable as a follow-up. Reciprocal Mapping was found to be significant in posttest scores, independent of gender and level of risk, and while holding the pretest scores constant. Findings showed there was a significant difference in the performance of the high-risk reading students taught with the Reciprocal Mapping intervention who scored statistically better than students in the control group. Further study findings showed that teacher fidelity of implementation of the treatment had a statistically significant relationship in predicting posttest scores when controlling for pretest scores. Study results indicated that improving students' use of text structure through the Reciprocal Mapping instructional routine positively supported sixth-grade students' social studies achievement.

A model of school managerial control : the systematic analysis of managerial behaviors, processes, and indicators

The theoretical construct of control has been defined as necessary (Etzioni, 1965), ubiquitous (Vickers, 1967), and on-going (E. Langer, 1983). Empirical measures, however, have not adequately given meaning to this potent construct, especially within complex organizations such as schools. Four stages of theory-development and empirical testing of school building managerial control using principals and teachers working within the nation's fourth largest district are presented in this dissertation as follows: (1) a review and synthesis of social science theories of control across the literatures of organizational theory, political science, sociology, psychology, and philosophy; (2) a systematic analysis of school managerial activities performed at the building level within the context of curricular and instructional tasks; (3) the development of a survey questionnaire to measure school building managerial control; and (4) initial tests of construct validity including inter-item reliability statistics, principal components analyses, and multivariate tests of significance. The social science synthesis provided support of four managerial control processes: standards, information, assessment, and incentives. The systematic analysis of school managerial activities led to further categorization between structural frequency of behaviors and discretionary qualities of behaviors across each of the control processes and the curricular and instructional tasks. Teacher survey responses (N=486) reported a significant difference between these two dimensions of control, structural frequency and discretionary qualities, for standards, information, and assessments, but not for incentives. The descriptive model of school managerial control suggests that (1) teachers perceive structural and discretionary managerial behaviors under information and incentives more clearly than activities representing standards or assessments, (2) standards are primarily structural while assessments are primarily qualitative, (3) teacher satisfaction is most closely related to the equitable distribution of incentives, (4) each of the structural managerial behaviors has a qualitative effect on teachers, and that (5) certain qualities of managerial behaviors are perceived by teachers as distinctly discretionary, apart from school structure. The variables of teacher tenure and school effectiveness reported significant effects on school managerial control processes, while instructional levels (elementary, junior, and senior) and individual school differences were not found to be significant for the construct of school managerial control.

Applications of capillary electrophoresis and mass spectrometry for the analysis of thiosalts

Thiosalt species are unstable, partially oxidized sulfur oxyanions formed in sulfur-rich environments but also during the flotation and milling of sulfidic minerals especially those containing pyrite (FeS₂) and pyrrhotite (Fe₍₁₋ₓ₎S, x = 0 to 0.2). Detecting and quantifying the major thiosalt species such as sulfate (SO₄²⁻), thiosulfate (S₂O₃²⁻), trithionate (S₃O₆²⁻), tetrathionate (S₄O₆²⁻) and higher polythionates (SₓO₆²⁻, where 3 ≤ x ≤ 10) in the milling process and in the treated tailings is important to understand how thiosalts are generated and provides insight into potential treatment. As these species are unstable, a fast and reliable analytical technique is required for their analysis. Three capillary zone electrophoresis (CZE) methods using indirect UV-vis detection were developed for the simultaneous separation and determination of five thiosalt anions: SO₄²⁻, S₂O₃²⁻, S₃O₆²⁻, S₄O₆²⁻ and S₅O₆²⁻. Both univariate and multivariate experimental design approaches were used to optimize the most critical factors (background electrolyte (BGE) and instrumental conditions) to achieve fast separation and quantitative analysis of the thiosalt species. The mathematically predicted responses for the multivariate experiments were in good agreement with the experimental results. Limits of detection (LODs) (S/N = 3) for the methods were between 0.09 and 0.34 μg/mL without a sample stacking technique and nearly four-fold increase in LODs with the application of field-amplified sample stacking. As direct analysis of thiosalts by mass spectrometry (MS) is limited by their low m/z values and detection in negative mode electrospray ionization (ESI), which is typically less sensitive than positive ESI, imidazolium-based (IP-L-Imid and IP-T-Imid) and phosphonium-based (IP-T-Phos) tricationic ion-pairing reagents were used to form stable high mass ions non-covalent +1 ion-pairs with these species for ESI-MS analysis and the association constants (Kassoc) determined for these ion-pairs. Kassoc values were between 6.85 × 10² M⁻¹ and 3.56 × 10⁵ M⁻¹ with the linear IP-L-Imid; 1.89 ×10³ M⁻¹ and 1.05 × 10⁵ M⁻¹ with the trigonal IP-T-Imid ion-pairs; and 7.51×10² M⁻¹ and 4.91× 10⁴ M⁻¹ with the trigonal IP-T-Phos ion-pairs. The highest formation constants were obtained for S₃O₆²⁻ and the imidazolium-based linear ion-pairing reagent (IP-L-Imid), whereas the lowest were for IP-L-Imid: SO₄²⁻ ion-pair.

Principal Component Analysis of Results Obtained from Finite-Difference Time-Domain Algorithms

Finite-Differences Time-Domain (FDTD) algorithms are well established tools of computational electromagnetism. Because of their practical implementation as computer codes, they are affected by many numerical artefact and noise. In order to obtain better results we propose using Principal Component Analysis (PCA) based on multivariate statistical techniques. The PCA has been successfully used for the analysis of noise and spatial temporal structure in a sequence of images. It allows a straightforward discrimination between the numerical noise and the actual electromagnetic variables, and the quantitative estimation of their respective contributions. Besides, The GDTD results can be filtered to clean the effect of the noise. In this contribution we will show how the method can be applied to several FDTD simulations: the propagation of a pulse in vacuum, the analysis of two-dimensional photonic crystals. In this last case, PCA has revealed hidden electromagnetic structures related to actual modes of the photonic crystal.

Raman Analysis of Dilute Aqueous Samples by Localized Evaporation of Submicroliter Droplets on the Tips of Superhydrophobic Copper Wires

Raman analysis of dilute aqueous solutions is normally prevented by their low signal levels. A very general method to increase the concentration to detectable levels is to evaporate droplets of the sample to dryness, creating solid deposits which are then Raman probed. Here, superhydrophobic (SHP) wires with hydrophilic tips have been used as supports for drying droplets, which have the advantage that the residue is automatically deposited at the tip. The SHP wires were readily prepared in minutes using electroless galvanic deposition of Ag onto copper wires followed by modification with a polyfluorothiol (3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro-1-decanethiol, HDFT). Cutting the coated wires with a scalpel revealed hydrophilic tips which could support droplets whose maximum size was determined by the wire diameter. Typically, 230 μm wires were used to support 0.6 μL droplets. Evaporation of dilute melamine droplets gave solid deposits which could be observed by scanning electron microscopy (SEM) and Raman spectroscopy. The limit of detection for melamine using a two stage evaporation procedure was 1 × 10^-6 mol dm^-3. The physical appearance of dried droplets of sucrose and glucose showed that the samples retained significant amounts of water, even under high vacuum. Nonetheless, the Raman detection limits of sucrose and glucose were 5 × 10^-4 and 2.5 × 10^-3 mol dm^-3, respectively, which is similar to the sensitivity reported for surface-enhanced Raman spectroscopy (SERS) detection of glucose. It was also possible to quantify the two sugars in mixtures at concentrations which were similar to those found in human blood through multivariate analysis.

Compositional data analysis of Holocene sediments from the West Bengal Sundarbans, India: Geochemical proxies for grain-size variability in a delta environment

This paper is part of a special issue of Applied Geochemistry focusing on reliable applications of compositional multivariate statistical methods. This study outlines the application of compositional data analysis (CoDa) to calibration of geochemical data and multivariate statistical modelling of geochemistry and grain-size data from a set of Holocene sedimentary cores from the Ganges-Brahmaputra (G-B) delta. Over the last two decades, understanding near-continuous records of sedimentary sequences has required the use of core-scanning X-ray fluorescence (XRF) spectrometry, for both terrestrial and marine sedimentary sequences. Initial XRF data are generally unusable in ‘raw-format’, requiring data processing in order to remove instrument bias, as well as informed sequence interpretation. The applicability of these conventional calibration equations to core-scanning XRF data are further limited by the constraints posed by unknown measurement geometry and specimen homogeneity, as well as matrix effects. Log-ratio based calibration schemes have been developed and applied to clastic sedimentary sequences focusing mainly on energy dispersive-XRF (ED-XRF) core-scanning. This study has applied high resolution core-scanning XRF to Holocene sedimentary sequences from the tidal-dominated Indian Sundarbans, (Ganges-Brahmaputra delta plain). The Log-Ratio Calibration Equation (LRCE) was applied to a sub-set of core-scan and conventional ED-XRF data to quantify elemental composition. This provides a robust calibration scheme using reduced major axis regression of log-ratio transformed geochemical data. Through partial least squares (PLS) modelling of geochemical and grain-size data, it is possible to derive robust proxy information for the Sundarbans depositional environment. The application of these techniques to Holocene sedimentary data offers an improved methodological framework for unravelling Holocene sedimentation patterns.

Development of Imaging Mass Spectrometry Analysis of Lipids in Biological and Clinically Relevant Applications

La spectrométrie de masse mesure la masse des ions selon leur rapport masse sur charge. Cette technique est employée dans plusieurs domaines et peut analyser des mélanges complexes. L’imagerie par spectrométrie de masse (Imaging Mass Spectrometry en anglais, IMS), une branche de la spectrométrie de masse, permet l’analyse des ions sur une surface, tout en conservant l’organisation spatiale des ions détectés. Jusqu’à présent, les échantillons les plus étudiés en IMS sont des sections tissulaires végétales ou animales. Parmi les molécules couramment analysées par l’IMS, les lipides ont suscité beaucoup d'intérêt. Les lipides sont impliqués dans les maladies et le fonctionnement normal des cellules; ils forment la membrane cellulaire et ont plusieurs rôles, comme celui de réguler des événements cellulaires. Considérant l’implication des lipides dans la biologie et la capacité du MALDI IMS à les analyser, nous avons développé des stratégies analytiques pour la manipulation des échantillons et l’analyse de larges ensembles de données lipidiques. La dégradation des lipides est très importante dans l’industrie alimentaire. De la même façon, les lipides des sections tissulaires risquent de se dégrader. Leurs produits de dégradation peuvent donc introduire des artefacts dans l’analyse IMS ainsi que la perte d’espèces lipidiques pouvant nuire à la précision des mesures d’abondance. Puisque les lipides oxydés sont aussi des médiateurs importants dans le développement de plusieurs maladies, leur réelle préservation devient donc critique. Dans les études multi-institutionnelles où les échantillons sont souvent transportés d’un emplacement à l’autre, des protocoles adaptés et validés, et des mesures de dégradation sont nécessaires. Nos principaux résultats sont les suivants : un accroissement en fonction du temps des phospholipides oxydés et des lysophospholipides dans des conditions ambiantes, une diminution de la présence des lipides ayant des acides gras insaturés et un effet inhibitoire sur ses phénomènes de la conservation des sections au froid sous N2. A température et atmosphère ambiantes, les phospholipides sont oxydés sur une échelle de temps typique d’une préparation IMS normale (~30 minutes). Les phospholipides sont aussi décomposés en lysophospholipides sur une échelle de temps de plusieurs jours. La validation d’une méthode de manipulation d’échantillon est d’autant plus importante lorsqu’il s’agit d’analyser un plus grand nombre d’échantillons. L’athérosclérose est une maladie cardiovasculaire induite par l’accumulation de matériel cellulaire sur la paroi artérielle. Puisque l’athérosclérose est un phénomène en trois dimension (3D), l'IMS 3D en série devient donc utile, d'une part, car elle a la capacité à localiser les molécules sur la longueur totale d’une plaque athéromateuse et, d'autre part, car elle peut identifier des mécanismes moléculaires du développement ou de la rupture des plaques. l'IMS 3D en série fait face à certains défis spécifiques, dont beaucoup se rapportent simplement à la reconstruction en 3D et à l’interprétation de la reconstruction moléculaire en temps réel. En tenant compte de ces objectifs et en utilisant l’IMS des lipides pour l’étude des plaques d’athérosclérose d’une carotide humaine et d’un modèle murin d’athérosclérose, nous avons élaboré des méthodes «open-source» pour la reconstruction des données de l’IMS en 3D. Notre méthodologie fournit un moyen d’obtenir des visualisations de haute qualité et démontre une stratégie pour l’interprétation rapide des données de l’IMS 3D par la segmentation multivariée. L’analyse d’aortes d’un modèle murin a été le point de départ pour le développement des méthodes car ce sont des échantillons mieux contrôlés. En corrélant les données acquises en mode d’ionisation positive et négative, l’IMS en 3D a permis de démontrer une accumulation des phospholipides dans les sinus aortiques. De plus, l’IMS par AgLDI a mis en évidence une localisation différentielle des acides gras libres, du cholestérol, des esters du cholestérol et des triglycérides. La segmentation multivariée des signaux lipidiques suite à l’analyse par IMS d’une carotide humaine démontre une histologie moléculaire corrélée avec le degré de sténose de l’artère. Ces recherches aident à mieux comprendre la complexité biologique de l’athérosclérose et peuvent possiblement prédire le développement de certains cas cliniques. La métastase au foie du cancer colorectal (Colorectal cancer liver metastasis en anglais, CRCLM) est la maladie métastatique du cancer colorectal primaire, un des cancers le plus fréquent au monde. L’évaluation et le pronostic des tumeurs CRCLM sont effectués avec l’histopathologie avec une marge d’erreur. Nous avons utilisé l’IMS des lipides pour identifier les compartiments histologiques du CRCLM et extraire leurs signatures lipidiques. En exploitant ces signatures moléculaires, nous avons pu déterminer un score histopathologique quantitatif et objectif et qui corrèle avec le pronostic. De plus, par la dissection des signatures lipidiques, nous avons identifié des espèces lipidiques individuelles qui sont discriminants des différentes histologies du CRCLM et qui peuvent potentiellement être utilisées comme des biomarqueurs pour la détermination de la réponse à la thérapie. Plus spécifiquement, nous avons trouvé une série de plasmalogènes et sphingolipides qui permettent de distinguer deux différents types de nécrose (infarct-like necrosis et usual necrosis en anglais, ILN et UN, respectivement). L’ILN est associé avec la réponse aux traitements chimiothérapiques, alors que l’UN est associé au fonctionnement normal de la tumeur.

FTIR, a potential tool to dementia diagnosis trough analysis of plasma

Nowadays it is still difficult to perform an early and accurate diagnosis of dementia, therefore many research focus on the finding of new dementia biomarkers that can aid in that purpose. So scientists try to find a noninvasive, rapid, and relatively inexpensive procedures for early diagnosis purpose. Several studies demonstrated that the utilization of spectroscopic techniques, such as Fourier Transform Infrared Spectroscopy (FTIR) and Raman spectroscopy could be an useful and accurate procedure to diagnose dementia. As several biochemical mechanisms related to neurodegeneration and dementia can lead to changes in plasma components and others peripheral body fluids, blood-based samples and spectroscopic analyses can be used as a more simple and less invasive technique. This work is intended to confirm some of the hypotheses of previous studies in which FTIR was used in the study of plasma samples of possible patient with AD and respective controls and verify the reproducibility of this spectroscopic technique in the analysis of such samples. Through the spectroscopic analysis combined with multivariate analysis it is possible to discriminate controls and demented samples and identify key spectroscopic differences between these two groups of samples which allows the identification of metabolites altered in this disease. It can be concluded that there are three spectral regions, 3500-2700 cm -1, 1800-1400 cm-1 and 1200-900 cm-1 where it can be extracted relevant spectroscopic information. In the first region, the main conclusion that is possible to take is that there is an unbalance between the content of saturated and unsaturated lipids. In the 1800-1400 cm-1 region it is possible to see the presence of protein aggregates and the change in protein conformation for highly stable parallel β-sheet. The last region showed the presence of products of lipid peroxidation related to impairment of membranes, and nucleic acids oxidative damage. FTIR technique and the information gathered in this work can be used in the construction of classification models that may be used for the diagnosis of cognitive dysfunction.

Health-related quality of life and determinant factors in celiac disease: a population-based analysis of adult patients in Spain

Background: Celiac disease (CD) has a negative impact on the health-related quality of life (HRQL) of affected patients. Although HRQL and its determinants have been examined in Spanish CD patients specifically recruited in hospital settings, these aspects of CD have not been assessed among the general Spanish population. Methods: An observational, cross-sectional study of a non-randomized, representative sample of adult celiac patients throughout all of Spain's Autonomous Regions. Subjects were recruited through celiac patient associations. A Spanish version of the self-administered Celiac Disease-Quality of Life (CD-QOL) questionnaire was used. Determinant factors of HRQL were assessed with the aid of multivariate analysis to control for confounding factors. Results: We analyzed the responses provided by 1,230 patients, 1,092 (89.2%) of whom were women. The overall mean value for the CD-QOL index was 56.3 ± 18.27 points. The dimension that obtained the most points was dysphoria, with 81.3 ± 19.56 points, followed by limitations with 52.3 ± 23.43 points; health problems, with 51.6 ± 26.08 points, and inadequate treatment, with 36.1 ± 21.18 points. Patient age and sex, along with time to diagnosis, and length of time on a gluten-free diet were all independent determinant factors of certain dimensions of HRQL: women aged 31 to 40 expressed poorer HRQL while time to diagnosis and length of time on a gluten-free diet were determinant factors for better HRQL scores. Conclusions: The HRQL level of adult Spanish celiac subjects is moderate, improving with the length of time patients remain on a gluten-free diet.

Development of Imaging Mass Spectrometry Analysis of Lipids in Biological and Clinically Relevant Applications

La spectrométrie de masse mesure la masse des ions selon leur rapport masse sur charge. Cette technique est employée dans plusieurs domaines et peut analyser des mélanges complexes. L’imagerie par spectrométrie de masse (Imaging Mass Spectrometry en anglais, IMS), une branche de la spectrométrie de masse, permet l’analyse des ions sur une surface, tout en conservant l’organisation spatiale des ions détectés. Jusqu’à présent, les échantillons les plus étudiés en IMS sont des sections tissulaires végétales ou animales. Parmi les molécules couramment analysées par l’IMS, les lipides ont suscité beaucoup d'intérêt. Les lipides sont impliqués dans les maladies et le fonctionnement normal des cellules; ils forment la membrane cellulaire et ont plusieurs rôles, comme celui de réguler des événements cellulaires. Considérant l’implication des lipides dans la biologie et la capacité du MALDI IMS à les analyser, nous avons développé des stratégies analytiques pour la manipulation des échantillons et l’analyse de larges ensembles de données lipidiques. La dégradation des lipides est très importante dans l’industrie alimentaire. De la même façon, les lipides des sections tissulaires risquent de se dégrader. Leurs produits de dégradation peuvent donc introduire des artefacts dans l’analyse IMS ainsi que la perte d’espèces lipidiques pouvant nuire à la précision des mesures d’abondance. Puisque les lipides oxydés sont aussi des médiateurs importants dans le développement de plusieurs maladies, leur réelle préservation devient donc critique. Dans les études multi-institutionnelles où les échantillons sont souvent transportés d’un emplacement à l’autre, des protocoles adaptés et validés, et des mesures de dégradation sont nécessaires. Nos principaux résultats sont les suivants : un accroissement en fonction du temps des phospholipides oxydés et des lysophospholipides dans des conditions ambiantes, une diminution de la présence des lipides ayant des acides gras insaturés et un effet inhibitoire sur ses phénomènes de la conservation des sections au froid sous N2. A température et atmosphère ambiantes, les phospholipides sont oxydés sur une échelle de temps typique d’une préparation IMS normale (~30 minutes). Les phospholipides sont aussi décomposés en lysophospholipides sur une échelle de temps de plusieurs jours. La validation d’une méthode de manipulation d’échantillon est d’autant plus importante lorsqu’il s’agit d’analyser un plus grand nombre d’échantillons. L’athérosclérose est une maladie cardiovasculaire induite par l’accumulation de matériel cellulaire sur la paroi artérielle. Puisque l’athérosclérose est un phénomène en trois dimension (3D), l'IMS 3D en série devient donc utile, d'une part, car elle a la capacité à localiser les molécules sur la longueur totale d’une plaque athéromateuse et, d'autre part, car elle peut identifier des mécanismes moléculaires du développement ou de la rupture des plaques. l'IMS 3D en série fait face à certains défis spécifiques, dont beaucoup se rapportent simplement à la reconstruction en 3D et à l’interprétation de la reconstruction moléculaire en temps réel. En tenant compte de ces objectifs et en utilisant l’IMS des lipides pour l’étude des plaques d’athérosclérose d’une carotide humaine et d’un modèle murin d’athérosclérose, nous avons élaboré des méthodes «open-source» pour la reconstruction des données de l’IMS en 3D. Notre méthodologie fournit un moyen d’obtenir des visualisations de haute qualité et démontre une stratégie pour l’interprétation rapide des données de l’IMS 3D par la segmentation multivariée. L’analyse d’aortes d’un modèle murin a été le point de départ pour le développement des méthodes car ce sont des échantillons mieux contrôlés. En corrélant les données acquises en mode d’ionisation positive et négative, l’IMS en 3D a permis de démontrer une accumulation des phospholipides dans les sinus aortiques. De plus, l’IMS par AgLDI a mis en évidence une localisation différentielle des acides gras libres, du cholestérol, des esters du cholestérol et des triglycérides. La segmentation multivariée des signaux lipidiques suite à l’analyse par IMS d’une carotide humaine démontre une histologie moléculaire corrélée avec le degré de sténose de l’artère. Ces recherches aident à mieux comprendre la complexité biologique de l’athérosclérose et peuvent possiblement prédire le développement de certains cas cliniques. La métastase au foie du cancer colorectal (Colorectal cancer liver metastasis en anglais, CRCLM) est la maladie métastatique du cancer colorectal primaire, un des cancers le plus fréquent au monde. L’évaluation et le pronostic des tumeurs CRCLM sont effectués avec l’histopathologie avec une marge d’erreur. Nous avons utilisé l’IMS des lipides pour identifier les compartiments histologiques du CRCLM et extraire leurs signatures lipidiques. En exploitant ces signatures moléculaires, nous avons pu déterminer un score histopathologique quantitatif et objectif et qui corrèle avec le pronostic. De plus, par la dissection des signatures lipidiques, nous avons identifié des espèces lipidiques individuelles qui sont discriminants des différentes histologies du CRCLM et qui peuvent potentiellement être utilisées comme des biomarqueurs pour la détermination de la réponse à la thérapie. Plus spécifiquement, nous avons trouvé une série de plasmalogènes et sphingolipides qui permettent de distinguer deux différents types de nécrose (infarct-like necrosis et usual necrosis en anglais, ILN et UN, respectivement). L’ILN est associé avec la réponse aux traitements chimiothérapiques, alors que l’UN est associé au fonctionnement normal de la tumeur.

Crowdfunding for entrepreneurship: an exploratory multivariate analysis concerning kickstarter and indiegogo platforms

The general purpose of this work is to describe and analyse the financing phenomenon of crowdfunding and to investigate the relations among crowdfunders, project creators and crowdfunding websites. More specifically, it also intends to describe the profile differences between major crowdfunding platforms, such as Kickstarter and Indiegogo. The findings are supported by literature, gathered from different scientific research papers. In the empirical part, data about Kickstarter and Indiegogo was collected from their websites and also complemented with further data from other statistical websites. For finding out specific information, such as satisfaction of entrepreneurs from both platforms, a satisfaction survey was applied among 200 entrepreneurs from different countries. To identify the profile of users of the Kickstarter and of the Indiegogo platforms, a multivariate analysis was performed, using a Hierarchical Clusters Analysis for each platform under study. Descriptive analysis was used for exploring information about popularity of platforms, average cost and the most popular area of projects, profile of users and future opportunities of platforms. To assess differences between groups, association between variables, and answering to the research hypothesis, an inferential analysis it was applied. The results showed that the Kickstarter and Indiegogo are one of the most popular crowdfunding platforms. Both of them have thousands of users and they are generally satisfied. Each of them uses individual approach for crowdfunders. Despite this, they both could benefit from further improving their services. Furthermore, according the results it was possible to observe that there is a direct and positive relationship between the money needed for the projects and the money collected from the investors for the projects, per platform.