Generalización de variables medioambientales mediante interpolación GIS

La investigación de esta tesis se centra en el estudio de técnicas geoestadísticas y su contribución a una mayor caracterización del binomio factores climáticos-rendimiento de un cultivo agrícola. El inexorable vínculo entre la variabilidad climática y la producción agrícola cobra especial relevancia en estudios sobre el cambio climático o en la modelización de cultivos para dar respuesta a escenarios futuros de producción mundial. Es información especialmente valiosa en sistemas operacionales de monitoreo y predicción de rendimientos de cultivos Los cuales son actualmente uno de los pilares operacionales en los que se sustenta la agricultura y seguridad alimentaria mundial; ya que su objetivo final es el de proporcionar información imparcial y fiable para la regularización de mercados. Es en este contexto, donde se quiso dar un enfoque alternativo a estudios, que con distintos planteamientos, analizan la relación inter-anual clima vs producción. Así, se sustituyó la dimensión tiempo por la espacio, re-orientando el análisis estadístico de correlación interanual entre rendimiento y factores climáticos, por el estudio de la correlación inter-regional entre ambas variables. Se utilizó para ello una técnica estadística relativamente nueva y no muy aplicada en investigaciones similares, llamada regresión ponderada geográficamente (GWR, siglas en inglés de “Geographically weighted regression”). Se obtuvieron superficies continuas de las variables climáticas acumuladas en determinados periodos fenológicos, que fueron seleccionados por ser factores clave en el desarrollo vegetativo de un cultivo. Por ello, la primera parte de la tesis, consistió en un análisis exploratorio sobre comparación de Métodos de Interpolación Espacial (MIE). Partiendo de la hipótesis de que existe la variabilidad espacial de la relación entre factores climáticos y rendimiento, el objetivo principal de esta tesis, fue el de establecer en qué medida los MIE y otros métodos geoestadísticos de regresión local, pueden ayudar por un lado, a alcanzar un mayor entendimiento del binomio clima-rendimiento del trigo blando (Triticum aestivum L.) al incorporar en dicha relación el componente espacial; y por otro, a caracterizar la variación de los principales factores climáticos limitantes en el crecimiento del trigo blando, acumulados éstos en cuatro periodos fenológicos. Para lleva a cabo esto, una gran carga operacional en la investigación de la tesis consistió en homogeneizar y hacer los datos fenológicos, climáticos y estadísticas agrícolas comparables tanto a escala espacial como a escala temporal. Para España y los Bálticos se recolectaron y calcularon datos diarios de precipitación, temperatura máxima y mínima, evapotranspiración y radiación solar en las estaciones meteorológicas disponibles. Se dispuso de una serie temporal que coincidía con los mismos años recolectados en las estadísticas agrícolas, es decir, 14 años contados desde 2000 a 2013 (hasta 2011 en los Bálticos). Se superpuso la malla de información fenológica de cuadrícula 25 km con la ubicación de las estaciones meteorológicas con el fin de conocer los valores fenológicos en cada una de las estaciones disponibles. Hecho esto, para cada año de la serie temporal disponible se calcularon los valores climáticos diarios acumulados en cada uno de los cuatro periodos fenológicos seleccionados P1 (ciclo completo), P2 (emergencia-madurez), P3 (floración) y P4 (floraciónmadurez). Se calculó la superficie interpolada por el conjunto de métodos seleccionados en la comparación: técnicas deterministas convencionales, kriging ordinario y cokriging ordinario ponderado por la altitud. Seleccionados los métodos más eficaces, se calculó a nivel de provincias las variables climatológicas interpoladas. Y se realizaron las regresiones locales GWR para cuantificar, explorar y modelar las relaciones espaciales entre el rendimiento del trigo y las variables climáticas acumuladas en los cuatro periodos fenológicos. Al comparar la eficiencia de los MIE no destaca una técnica por encima del resto como la que proporcione el menor error en su predicción. Ahora bien, considerando los tres indicadores de calidad de los MIE estudiados se han identificado los métodos más efectivos. En el caso de la precipitación, es la técnica geoestadística cokriging la más idónea en la mayoría de los casos. De manera unánime, la interpolación determinista en función radial (spline regularizado) fue la técnica que mejor describía la superficie de precipitación acumulada en los cuatro periodos fenológicos. Los resultados son más heterogéneos para la evapotranspiración y radiación. Los métodos idóneos para estas se reparten entre el Inverse Distance Weighting (IDW), IDW ponderado por la altitud y el Ordinary Kriging (OK). También, se identificó que para la mayoría de los casos en que el error del Ordinary CoKriging (COK) era mayor que el del OK su eficacia es comparable a la del OK en términos de error y el requerimiento computacional de este último es mucho menor. Se pudo confirmar que existe la variabilidad espacial inter-regional entre factores climáticos y el rendimiento del trigo blando tanto en España como en los Bálticos. La herramienta estadística GWR fue capaz de reproducir esta variabilidad con un rendimiento lo suficientemente significativo como para considerarla una herramienta válida en futuros estudios. No obstante, se identificaron ciertas limitaciones en la misma respecto a la información que devuelve el programa a nivel local y que no permite desgranar todo el detalle sobre la ejecución del mismo. Los indicadores y periodos fenológicos que mejor pudieron reproducir la variabilidad espacial del rendimiento en España y Bálticos, arrojaron aún, una mayor credibilidad a los resultados obtenidos y a la eficacia del GWR, ya que estaban en línea con el conocimiento agronómico sobre el cultivo del trigo blando en sistemas agrícolas mediterráneos y norteuropeos. Así, en España, el indicador más robusto fue el balance climático hídrico Climatic Water Balance) acumulado éste, durante el periodo de crecimiento (entre la emergencia y madurez). Aunque se identificó la etapa clave de la floración como el periodo en el que las variables climáticas acumuladas proporcionaban un mayor poder explicativo del modelo GWR. Sin embargo, en los Bálticos, países donde el principal factor limitante en su agricultura es el bajo número de días de crecimiento efectivo, el indicador más efectivo fue la radiación acumulada a lo largo de todo el ciclo de crecimiento (entre la emergencia y madurez). Para el trigo en regadío no existe ninguna combinación que pueda explicar más allá del 30% de la variación del rendimiento en España. Poder demostrar que existe un comportamiento heterogéneo en la relación inter-regional entre el rendimiento y principales variables climáticas, podría contribuir a uno de los mayores desafíos a los que se enfrentan, a día de hoy, los sistemas operacionales de monitoreo y predicción de rendimientos de cultivos, y éste es el de poder reducir la escala espacial de predicción, de un nivel nacional a otro regional. ABSTRACT This thesis explores geostatistical techniques and their contribution to a better characterization of the relationship between climate factors and agricultural crop yields. The crucial link between climate variability and crop production plays a key role in climate change research as well as in crops modelling towards the future global production scenarios. This information is particularly important for monitoring and forecasting operational crop systems. These geostatistical techniques are currently one of the most fundamental operational systems on which global agriculture and food security rely on; with the final aim of providing neutral and reliable information for food market controls, thus avoiding financial speculation of nourishments of primary necessity. Within this context the present thesis aims to provide an alternative approach to the existing body of research examining the relationship between inter-annual climate and production. Therefore, the temporal dimension was replaced for the spatial dimension, re-orienting the statistical analysis of the inter-annual relationship between crops yields and climate factors to an inter-regional correlation between these two variables. Geographically weighted regression, which is a relatively new statistical technique and which has rarely been used in previous research on this topic was used in the current study. Continuous surface values of the climate accumulated variables in specific phenological periods were obtained. These specific periods were selected because they are key factors in the development of vegetative crop. Therefore, the first part of this thesis presents an exploratory analysis regarding the comparability of spatial interpolation methods (SIM) among diverse SIMs and alternative geostatistical methodologies. Given the premise that spatial variability of the relationship between climate factors and crop production exists, the primary aim of this thesis was to examine the extent to which the SIM and other geostatistical methods of local regression (which are integrated tools of the GIS software) are useful in relating crop production and climate variables. The usefulness of these methods was examined in two ways; on one hand the way this information could help to achieve higher production of the white wheat binomial (Triticum aestivum L.) by incorporating the spatial component in the examination of the above-mentioned relationship. On the other hand, the way it helps with the characterization of the key limiting climate factors of soft wheat growth which were analysed in four phenological periods. To achieve this aim, an important operational workload of this thesis consisted in the homogenization and obtention of comparable phenological and climate data, as well as agricultural statistics, which made heavy operational demands. For Spain and the Baltic countries, data on precipitation, maximum and minimum temperature, evapotranspiration and solar radiation from the available meteorological stations were gathered and calculated. A temporal serial approach was taken. These temporal series aligned with the years that agriculture statistics had previously gathered, these being 14 years from 2000 to 2013 (until 2011 for the Baltic countries). This temporal series was mapped with a phenological 25 km grid that had the location of the meteorological stations with the objective of obtaining the phenological values in each of the available stations. Following this procedure, the daily accumulated climate values for each of the four selected phenological periods were calculated; namely P1 (complete cycle), P2 (emergency-maturity), P3 (flowering) and P4 (flowering- maturity). The interpolated surface was then calculated using the set of selected methodologies for the comparison: deterministic conventional techniques, ordinary kriging and ordinary cokriging weighted by height. Once the most effective methods had been selected, the level of the interpolated climate variables was calculated. Local GWR regressions were calculated to quantify, examine and model the spatial relationships between soft wheat production and the accumulated variables in each of the four selected phenological periods. Results from the comparison among the SIMs revealed that no particular technique seems more favourable in terms of accuracy of prediction. However, when the three quality indicators of the compared SIMs are considered, some methodologies appeared to be more efficient than others. Regarding precipitation results, cokriging was the most accurate geostatistical technique for the majority of the cases. Deterministic interpolation in its radial function (controlled spline) was the most accurate technique for describing the accumulated precipitation surface in all phenological periods. However, results are more heterogeneous for the evapotranspiration and radiation methodologies. The most appropriate technique for these forecasts are the Inverse Distance Weighting (IDW), weighted IDW by height and the Ordinary Kriging (OK). Furthermore, it was found that for the majority of the cases where the Ordinary CoKriging (COK) error was larger than that of the OK, its efficacy was comparable to that of the OK in terms of error while the computational demands of the latter was much lower. The existing spatial inter-regional variability between climate factors and soft wheat production was confirmed for both Spain and the Baltic countries. The GWR statistic tool reproduced this variability with an outcome significative enough as to be considered a valid tool for future studies. Nevertheless, this tool also had some limitations with regards to the information delivered by the programme because it did not allow for a detailed break-down of its procedure. The indicators and phenological periods that best reproduced the spatial variability of yields in Spain and the Baltic countries made the results and the efficiency of the GWR statistical tool even more reliable, despite the fact that these were already aligned with the agricultural knowledge about soft wheat crop under mediterranean and northeuropean agricultural systems. Thus, for Spain, the most robust indicator was the Climatic Water Balance outcome accumulated throughout the growing period (between emergency and maturity). Although the flowering period was the phase that best explained the accumulated climate variables in the GWR model. For the Baltic countries where the main limiting agricultural factor is the number of days of effective growth, the most effective indicator was the accumulated radiation throughout the entire growing cycle (between emergency and maturity). For the irrigated soft wheat there was no combination capable of explaining above the 30% of variation of the production in Spain. The fact that the pattern of the inter-regional relationship between the crop production and key climate variables is heterogeneous within a country could contribute to one is one of the greatest challenges that the monitoring and forecasting operational systems for crop production face nowadays. The present findings suggest that the solution may lay in downscaling the spatial target scale from a national to a regional level.

Relationship among Corneal Biomechanics, Refractive Error, and Axial Length

Purpose: To evaluate the relationship between different ocular and corneal biomechanical parameters in emmetropic and ametropic healthy white children. Methods: This study included 293 eyes of 293 healthy Spanish children (135 boys and 158 girls), ranging in age from 6 to 17 years. Subjects were divided according to the refractive error: control (emmetropia, 99 children), myopia (100 children), and hyperopia (94 children) groups. In all cases, corneal hysteresis (CH) and corneal resistance factor (CRF) were evaluated with the Ocular Response Analyzer system. Axial length (AL) and mean corneal power were also measured by partial coherence interferometry (IOLMaster), and central corneal thickness (CCT) and anterior chamber depth were measured by anterior segment optical coherence tomography (Visante). Results: Mean (±SD) CH and CRF were 12.12 (±1.71) and 12.30 (±1.89) mm Hg, respectively. Mean (±SD) CCT was 542.68 (±37.20) μm and mean (±SD) spherical equivalent was +0.14 (±3.41) diopters. A positive correlation was found between CH and CRF (p < 0.001), and both correlated as well with CCT (p < 0.0001). Corneal resistance factor was found to decrease with increasing age (p = 0.01). Lower levels of CH were associated with longer AL and more myopia (p < 0.001 and p = 0.001, respectively). Higher values of CH were associated with increasing hyperopia. Significant differences in CH were found between emmetropic and myopic groups (p < 0.001) and between myopic and hyperopic groups (p = 0.011). There were also significant differences in CRF between emmetropic and myopic groups (p = 0.02). Multiple linear regression analysis showed that lower CH and CRF significantly associated with thinner CCT, longer AL, and flatter corneal curvature. Conclusions: The Ocular Response Analyzer corneal biomechanical properties seem to be compromised in myopia from an early age, especially in high myopia.

Estimation of the Central Corneal Power in Keratoconus: Theoretical and Clinical Assessment of the Error of the Keratometric Approach

Purpose: The aim of this study was to analyze theoretically the errors in the central corneal power calculation in eyes with keratoconus when a keratometric index (nk) is used and to clinically confirm the errors induced by this approach. Methods: Differences (DPc) between central corneal power estimation with the classical nk (Pk) and with the Gaussian equation (PGauss c ) in eyes with keratoconus were simulated and evaluated theoretically, considering the potential range of variation of the central radius of curvature of the anterior (r1c) and posterior (r2c) corneal surfaces. Further, these differences were also studied in a clinical sample including 44 keratoconic eyes (27 patients, age range: 14–73 years). The clinical agreement between Pk and PGauss c (true net power) obtained with a Scheimpflug photography–based topographer was evaluated in such eyes. Results: For nk = 1.3375, an overestimation was observed in most cases in the theoretical simulations, with DPc ranging from an underestimation of 20.1 diopters (D) (r1c = 7.9 mm and r2c = 8.2 mm) to an overestimation of 4.3 D (r1c = 4.7 mm and r2c = 3.1 mm). Clinically, Pk always overestimated the PGauss c given by the topography system in a range between 0.5 and 2.5 D (P , 0.01). The mean clinical DPc was 1.48 D, with limits of agreement of 0.71 and 2.25 D. A very strong statistically significant correlation was found between DPc and r2c (r = 20.93, P , 0.01). Conclusions: The use of a single value for nk for the calculation of corneal power is imprecise in keratoconus and can lead to significant clinical errors.

The relationship of cervical joint position error to balance and eye movement disturbances in persistent whiplash

Cervical joint position error (JPE) has been used as a measure of cervical afferent input to detect disturbances in sensori-motor control as a possible contributor to a neck pain syndrome. This study aimed to investigate the relationship between cervical JPE, balance and eye movement control. It was of particular interest whether assessment of cervical ME alone was sufficient to signal the presence of disturbances in the two other tests. One hundred subjects with persistent whiplash-associated disorders (WADs) and 40 healthy controls subjects were assessed on measures of cervical JPE, standing balance and the smooth pursuit neck torsion test (SPNT). The results indicated that over all subjects, significant but weak-to-moderate correlations existed between all comfortable stance balance tests and both the SPNT and rotation cervical ME tests. A weak correlation was found between the SPNT and right rotation cervical JPE. An abnormal rotation cervical JPE score had a high positive prediction value (88%) but low sensitivity (60%) and specificity (54%) to determine abnormality in balance and or SPNT test. The results suggest that in patients with persistent WAD, it is not sufficient to measure ME alone. All three measures are required to identify disturbances in the postural control system. (C) 2005 Elsevier Ltd. All rights reserved.

Data analysis methods in optometry. Part 5: correlation

1. Pearson's correlation coefficient only tests whether the data fit a linear model. With large numbers of observations, quite small values of r become significant and the X variable may only account for a minute proportion of the variance in Y. Hence, the value of r squared should always be calculated and included in a discussion of the significance of r. 2. The use of r assumes that a bivariate normal distribution is present and this assumption should be examined prior to the study. If Pearson's r is not appropriate, then a non-parametric correlation coefficient such as Spearman's rs may be used. 3. A significant correlation should not be interpreted as indicating causation especially in observational studies in which there is a high probability that the two variables are correlated because of their mutual correlations with other variables. 4. In studies of measurement error, there are problems in using r as a test of reliability and the ‘intra-class correlation coefficient’ should be used as an alternative. A correlation test provides only limited information as to the relationship between two variables. Fitting a regression line to the data using the method known as ‘least square’ provides much more information and the methods of regression and their application in optometry will be discussed in the next article.

Reduced attentional capacity, but normal processing speed and shifting of attention in developmental dyslexia: evidence from a serial task

We report the performance of a group of adult dyslexics and matched controls in an array-matching task where two strings of either consonants or symbols are presented side by side and have to be judged to be the same or different. The arrays may differ either in the order or identity of two adjacent characters. This task does not require naming – which has been argued to be the cause of dyslexics’ difficulty in processing visual arrays – but, instead, has a strong serial component as demonstrated by the fact that, in both groups, Reaction times (RTs) increase monotonically with position of a mismatch. The dyslexics are clearly impaired in all conditions and performance in the identity conditions predicts performance across orthographic tasks even after age, performance IQ and phonology are partialled out. Moreover, the shapes of serial position curves are revealing of the underlying impairment. In the dyslexics, RTs increase with position at the same rate as in the controls (lines are parallel) ruling out reduced processing speed or difficulties in shifting attention. Instead, error rates show a catastrophic increase for positions which are either searched later or more subject to interference. These results are consistent with a reduction in the attentional capacity needed in a serial task to bind together identity and positional information. This capacity is best seen as a reduction in the number of spotlights into which attention can be split to process information at different locations rather than as a more generic reduction of resources which would also affect processing the details of single objects.

Minimum Mean Square Error Approach in Images Processing for Full-field Displacements and Deformation Measurements

A vision system is applied to full-field displacements and deformation measurements in solid mechanics. A speckle like pattern is preliminary formed on the surface under investigation. To determine displacements field of one speckle image with respect to a reference speckle image, sub-images, referred to Zones Of Interest (ZOI) are considered. The field is obtained by matching a ZOI in the reference image with the respective ZOI in the moved image. Two image processing techniques are used for implementing the matching procedure: – cross correlation function and minimum mean square error (MMSE) of the ZOI intensity distribution. The two algorithms are compared and the influence of the ZOI size on the accuracy of measurements is studied.

Is pupil diameter influenced by refractive error?

Purpose: To investigate the relationship between pupil diameter and refractive error and how refractive correction, target luminance, and accommodation modulate this relationship. Methods: Sixty emmetropic, myopic, and hyperopic subjects (age range, 18 to 35 years) viewed an illuminated target (luminance: 10, 100, 200, 400, 1000, 2000, and 4100 cd/m2) within a Badal optical system, at 0 diopters (D) and −3 D vergence, with and without refractive correction. Refractive error was corrected using daily disposable contact lenses. Pupil diameter and accommodation were recorded continuously using a commercially available photorefractor. Results: No significant difference in pupil diameter was found between the refractive groups at 0 D or −3 D target vergence, in the corrected or uncorrected conditions. As expected, pupil diameter decreased with increasing luminance. Target vergence had no significant influence on pupil diameter. In the corrected condition, at 0 D target vergence, the accommodation response was similar in all refractive groups. At −3 D target vergence, the emmetropic and myopic groups accommodated significantly more than the hyperopic group at all luminance levels. There was no correlation between accommodation response and pupil diameter or refractive error in any refractive group. In the uncorrected condition, the accommodation response was significantly greater in the hyperopic group than in the myopic group at all luminance levels, particularly for near viewing. In the hyperopic group, the accommodation response was significantly correlated with refractive error but not pupil diameter. In the myopic group, accommodation response level was not correlated with refractive error or pupil diameter. Conclusions: Refractive error has no influence on pupil diameter, irrespective of refractive correction or accommodative demand. This suggests that the pupil is controlled by the pupillary light reflex and is not driven by retinal blur.

Intraoperative prediction of refractive error using a prototype surgical aberrometer

Purpose: To ascertain the agreement level between intra-operative refraction using a prototype surgical Hartmann-Shack aberrometer and subjective refraction a month later. Methods: Fifty-four consecutive patients had their pseudophakic refractive measured with the aberrometer intra-operatively at the end of their cataract surgery. A masked optometrist performed subjective refraction 4 weeks later. The two sets of data were then analysed for correlation. Results: The mean spherical equivalent was −0.14 ± 0.37 D (Range: −1.41 to +1.72 D) with the prototype aberrometer and −0.34 ± 0.32 (−1.64 to +1.88 D) with subjective refraction. The measurements positively correlated to a very high degree (r =+0.81, p < 0.01). In 84.3% of cases the two measurements were within 0.50D of each other. Conclusion: The aberrometer can verify the aimed refractive status of the eye intraoperatively to avoid a refractive surprise. The aberrometer is a useful tool for real time assessment of the ocular refractive status.

Three essays on entrepreneurial entry, serial entrepreneurship, and labor turnover

This study explores two important aspects of entrepreneurship — liquidity constraints and serial entrepreneurs, with an additional analysis of occupational choice among wage workers. In the first essay, I revisit the question of whether entrepreneurs face liquidity constraints in business formation. The principle challenge is that wealth is correlated with unobserved ability, and adequate instruments are often difficult to identify. This paper uses the son's birth order as an instrument for household wealth. I exploit the data available in the Korean Labor and Income Panel Study, and find evidence of liquidity constraints associated with self-employment in South Korea. The second essay develops and tests a model that explains entry into serial entrepreneurship and the performance of serial entrepreneurs as the result of selection on innate ability. The model supposes that agents establish businesses with imperfect information about their entrepreneurial ability and the profitability of business ideas. Agents continually observe signals with which they update their beliefs, and this process eventually determines their next business choice. Selection on ability induces a positive correlation between entrepreneurial experience (measured by previous business earnings and founding experience) and serial business formation, as well as its subsequent performance. The predictions in the model are tested using panel data from the NLSY79. The analysis permits a distinction to be made between selection on innate ability and learning by doing. Motivated by previous empirical findings that white-collar workers had higher turnover rates than blue-collar workers during firm expansion, the third essay further examines job turnover among workers with or without specific skills. I present a search-matching model, which predicts that when firm growth is driven by technological advance, workers whose skills are specific to the obsolete technology show a higher tendency to separate from their jobs. This hypothesis is tested with data from the PSID. I find supportive evidence that in the context of technological change, having an occupation requiring specific skills, such as computer specialists or engineers, increases the odds of job separation by nearly eight percent. ^

Serial evolutionary networks of within-patient HIV-1 sequences reveal patterns of evolution of X4 strains

Background The HIV virus is known for its ability to exploit numerous genetic and evolutionary mechanisms to ensure its proliferation, among them, high replication, mutation and recombination rates. Sliding MinPD, a recently introduced computational method [1], was used to investigate the patterns of evolution of serially-sampled HIV-1 sequence data from eight patients with a special focus on the emergence of X4 strains. Unlike other phylogenetic methods, Sliding MinPD combines distance-based inference with a nonparametric bootstrap procedure and automated recombination detection to reconstruct the evolutionary history of longitudinal sequence data. We present serial evolutionary networks as a longitudinal representation of the mutational pathways of a viral population in a within-host environment. The longitudinal representation of the evolutionary networks was complemented with charts of clinical markers to facilitate correlation analysis between pertinent clinical information and the evolutionary relationships. Results Analysis based on the predicted networks suggests the following:: significantly stronger recombination signals (p = 0.003) for the inferred ancestors of the X4 strains, recombination events between different lineages and recombination events between putative reservoir virus and those from a later population, an early star-like topology observed for four of the patients who died of AIDS. A significantly higher number of recombinants were predicted at sampling points that corresponded to peaks in the viral load levels (p = 0.0042). Conclusion Our results indicate that serial evolutionary networks of HIV sequences enable systematic statistical analysis of the implicit relations embedded in the topology of the structure and can greatly facilitate identification of patterns of evolution that can lead to specific hypotheses and new insights. The conclusions of applying our method to empirical HIV data support the conventional wisdom of the new generation HIV treatments, that in order to keep the virus in check, viral loads need to be suppressed to almost undetectable levels.

Correlation between pre-treatment quasispecies complexity and treatment outcome in chronic HCV genotype 3a

Pre-treatment HCV quasispecies complexity and diversity may predict response to interferon based anti-viral therapy. The objective of this study was to retrospectively (1) examine temporal changes in quasispecies prior to the start of therapy and (2) investigate extensively quasispecies evolution in a group of 10 chronically infected patients with genotype 3a, treated with pegylated alpha 2a-Interferon and ribavirin. The degree of sequence heterogeneity within the hypervariable region 1 was assessed by analyzing 20-30 individual clones in serial serum samples. Genetic parameters, including amino acid Shannon entropy, Hamming distance and genetic distance were calculated for each sample. Treatment outcome was divided into (1) sustained virological responders (SVR) and (2) treatment failure (TF).Our results indicate, (1) quasispecies complexity and diversity are lower in the SVR group, (2) quasispecies vary temporally and (3) genetic heterogeneity at baseline can be used to predict treatment outcome. We discuss the results from the perspective of replicative homeostasis. We discuss the results from the perspective of replicative homeostasis.

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.

Seasonality Shows Evidence for Polygenic Architecture and Genetic Correlation With Schizophrenia and Bipolar Disorder

OBJECTIVE: To test common genetic variants for association with seasonality (seasonal changes in mood and behavior) and to investigate whether there are shared genetic risk factors between psychiatric disorders and seasonality. METHOD: Genome-wide association studies (GWASs) were conducted in Australian (between 1988 and 1990 and between 2010 and 2013) and Amish (between May 2010 and December 2011) samples in whom the Seasonal Pattern Assessment Questionnaire (SPAQ) had been administered, and the results were meta-analyzed in a total sample of 4,156 individuals. Genetic risk scores based on results from prior large GWAS studies of bipolar disorder, major depressive disorder (MDD), and schizophrenia were calculated to test for overlap in risk between psychiatric disorders and seasonality. RESULTS: The most significant association was with rs11825064 (P = 1.7 × 10⁻⁶, β = 0.64, standard error = 0.13), an intergenic single nucleotide polymorphism (SNP) found on chromosome 11. The evidence for overlap in risk factors was strongest for schizophrenia and seasonality, with the schizophrenia genetic profile scores explaining 3% of the variance in log-transformed global seasonality scores. Bipolar disorder genetic profile scores were also associated with seasonality, although at much weaker levels (minimum P value = 3.4 × 10⁻³), and no evidence for overlap in risk was detected between MDD and seasonality. CONCLUSIONS: Common SNPs of large effect most likely do not exist for seasonality in the populations examined. As expected, there were overlapping genetic risk factors for bipolar disorder (but not MDD) with seasonality. Unexpectedly, the risk for schizophrenia and seasonality had the largest overlap, an unprecedented finding that requires replication in other populations and has potential clinical implications considering overlapping cognitive deficits in seasonal affective disorders and schizophrenia.

Effect of haptic guidance and error amplification robotic training interventions on the immediate improvement of timing among individuals that had a stroke

Abstract : Many individuals that had a stroke have motor impairments such as timing deficits that hinder their ability to complete daily activities like getting dressed. Robotic rehabilitation is an increasingly popular therapeutic avenue in order to improve motor recovery among this population. Yet, most studies have focused on improving the spatial aspect of movement (e.g. reaching), and not the temporal one (e.g. timing). Hence, the main aim of this study was to compare two types of robotic rehabilitation on the immediate improvement of timing accuracy: haptic guidance (HG), which consists of guiding the person to make the correct movement, and thus decreasing his or her movement errors, and error amplification (EA), which consists of increasing the person’s movement errors. The secondary objective consisted of exploring whether the side of the stroke lesion had an effect on timing accuracy following HG and EA training. Thirty-four persons that had a stroke (average age 67 ± 7 years) participated in a single training session of a timing-based task (simulated pinball-like task), where they had to activate a robot at the correct moment to successfully hit targets that were presented a random on a computer screen. Participants were randomly divided into two groups, receiving either HG or EA. During the same session, a baseline phase and a retention phase were given before and after each training, and these phases were compared in order to evaluate and compare the immediate impact of HG and EA on movement timing accuracy. The results showed that HG helped improve the immediate timing accuracy (p=0.03), but not EA (p=0.45). After comparing both trainings, HG was revealed to be superior to EA at improving timing (p=0.04). Furthermore, a significant correlation was found between the side of stroke lesion and the change in timing accuracy following EA (r[subscript pb]=0.7, p=0.001), but not HG (r[subscript pb]=0.18, p=0.24). In other words, a deterioration in timing accuracy was found for participants with a lesion in the left hemisphere that had trained with EA. On the other hand, for the participants having a right-sided stroke lesion, an improvement in timing accuracy was noted following EA. In sum, it seems that HG helps improve the immediate timing accuracy for individuals that had a stroke. Still, the side of the stroke lesion seems to play a part in the participants’ response to training. This remains to be further explored, in addition to the impact of providing more training sessions in order to assess any long-term benefits of HG or EA.