Pilar Zuluaga

Complexity analysis of spontaneous brain activity in attention-deficit/hyperactivity disorder: diagnostic implications.

BACKGROUND Attention-deficit/hyperactivity disorder (ADHD) is defined as the most common neurobehavioral disorder of childhood, but an objective diagnostic test is not available yet to date. Neurophychological, neuroimaging, and neurophysiological research offer ample evidence of brain and behavioral dysfunctions in ADHD, but these findings have not been useful as a diagnostic test. METHODS Whole-head magnetoencephalographic recordings were obtained from 14 diagnosed ADHD patients and 14 healthy children during resting conditions. Lempel-Ziv complexity (LZC) values were obtained for each channel and child and averaged in five sensor groups: anterior, central, left lateral, right lateral, and posterior. RESULTS Lempel-Ziv complexity scores were significantly higher in control subjects, with the maximum value in anterior region. Combining age and anterior complexity values allowed the correct classification of ADHD patients and control subjects with a 93% sensitivity and 79% specificity. Control subjects showed an age-related monotonic increase of LZC scores in all sensor groups, while children with ADHD exhibited a nonsignificant tendency toward decreased LZC scores. The age-related divergence resulted in a 100% specificity in children older than 9 years. CONCLUSIONS Results support the role of a frontal hypoactivity in the diagnosis of ADHD. Moreover, the age-related divergence of complexity scores between ADHD patients and control subjects might reflect distinctive developmental trajectories. This interpretation of our results is in agreement with recent investigations reporting a delay of cortical maturation in the prefrontal cortex.

Complexity analysis of spontaneous brain activity: effects of depression and antidepressant treatment:

Magnetoencephalography (MEG) allows the real-time recording of neural activity and oscillatory activity in distributed neural networks. We applied a non-linear complexity analysis to resting-state neural activity as measured using whole-head MEG. Recordings were obtained from 20 unmedicated patients with major depressive disorder and 19 matched healthy controls. Subsequently, after 6 months of pharmacological treatment with the antidepressant mirtazapine 30 mg/day, patients received a second MEG scan. A measure of the complexity of neural signals, the Lempel–Ziv Complexity (LZC), was derived from the MEG time series. We found that depressed patients showed higher pre-treatment complexity values compared with controls, and that complexity values decreased after 6 months of effective pharmacological treatment, although this effect was statistically significant only in younger patients. The main treatment effect was to recover the tendency observed in controls of a positive correlation between age and complexity values. Importantly, the reduction of complexity with treatment correlated with the degree of clinical symptom remission. We suggest that LZC, a formal measure of neural activity complexity, is sensitive to the dynamic physiological changes observed in depression and may potentially offer an objective marker of depression and its remission after treatment.

Quantitative modeling of peptide binding to TAP using support vector machine

The transport of peptides to the endoplasmic reticulum by the transporter associated with antigen processing (TAP) is a necessary step towards determining CD8 T cell epitopes. In this work, we have studied the predictive performance of support vector machine models trained on single residue positions and residue combinations drawn from a large dataset consisting of 613 nonamer peptides of known affinity to TAP. Predictive performance of these TAP affinity models was evaluated under 10‐fold cross‐validation experiments and measured using Pearsons correlation coefficients (Rp). Our results show that every peptide position (P1–P9) contributes to TAP binding (minimum Rp of 0.26 ± 0.11 was achieved by a model trained on the P6 residue), although the largest contributions to binding correspond to the C‐terminal end (Rp = 0.68 ± 0.06) and the P1 (Rp = 0.51 ± 0.09) and P2 (0.57 ± 0.08) residues of the peptide. Training the models on additional peptide residues generally improved their predictive performance and a maximum correlation (Rp = 0.89 ± 0.03) was achieved by a model trained on the full‐length sequences or a residue selection consisting of the first 5 N‐ and last 3 C‐terminal residues of the peptides included in the training set. A system for predicting the binding affinity of peptides to TAP using the methods described here is readily available for free public use at http://imed.med.ucm.es/Tools/tapreg/. Proteins 2010.

Factors associated with recent increase of multiple births in Spain.

The increased incidence of multiple deliveries in Spain, in addition to changes in age at maternity and parity, is attributed to assisted reproductive treatments, but the relative contribution of the latter to this rise remains uncertain, due to the scarce information provided by clinics practicing those treatments. Population based data (1984-2004), including information on mothers age, nationality, marital status, date of delivery, and the characteristics of each (parity, single or multiple), and sex of newborns were provided by the Spanish Institute of Statistics. Twinning and triplet deliveries relate to maternal age, parity, and nationality. For younger ages (<or= 19, 20-24, 25-29) rates remained constant over time, but for older women (30-34, 35-39, >or= 40) rates increased after 1994. From 1984 to 2004 the percentage of twins of opposite sex increased from 24.31 to 36.58 per cent. Since 1997, Spanish and non-Spanish mothers differentiate with respect to multiple maternity at ages over 30. In addition to unmarried Spanish women, immigrants constitute a reliable reference group that determines the convenience of segregating information on multiple deliveries respecting origin. The proportion of twins and triplets of opposite sex, maternal age, and parity patterns observed are concordant with a differential access to reproductive treatments depending on the womans age. The present norm regulating the maximum number of fertilizations per cycle and the demand for these treatments explain the high incidence of multiple deliveries in Spain. A modified logistic curve predicts a stabilization of multiple deliveries, which will probably continue to be high in Spain.

EQUIVALENCE BETWEEN SCORE AND WEIGHTED TESTS FOR SURVIVAL CURVES

In this paper we describe 10 expressions of score and weighted tests, in such a way that the numerators and the denominators are completely specified, including always the possibility of tied observations. We establish the equivalence between score and weighted tests in the general setting of ties. Based upon this equivalence we enunciate two new tests, which complete the jigsaw of the classification of these non-parametric tests in Survival Analysis.

Dipole density of low-frequency and spike magnetic activity: a reliable procedure in presurgical evaluation of temporal lobe epilepsy.

Conventional visual analysis and dipole density analysis of magnetoencephalographic data for both spike and low-frequency magnetic activity were compared for presurgical evaluation in temporal lobe epilepsy (TLE) in a sample of 26 drug-resistant operated TLE patients. A series of logistic regression analyses were performed. Dipole density sensitivity was superior to visual localization analysis. Three separated logistic models were calculated for interictal spikes, low-frequency magnetic activity, and the combination of both measures. A combined interictal spike/low-frequency magnetic activity model predicted correctly the operated temporal lobe in all patients. Clear-cut criteria for the probability model are proposed that are valid for 92.3% of cases in the sample. The quantitative approach proposed by this study is an evidence-based model for presurgical evaluation of temporal lobe epilepsy, which improves previous magnetoencephalographic investigations and establishes working clinical criteria for patient evaluation in TLE.

Immunocytochemical detection of synaptophysin in C57BL/6 mice cochlea during aging process

Aged mammals frequently exhibit a bilateral, progressive, and symmetric deafness related to the degeneration of auditory receptor. However, little is still known about aging effects on synapses in this receptor. Synaptophysin (Syp) is a 38 kDa Ca2+ binding glycoprotein widely found in presynaptic membrane and vesicles. The Syp has been found in presynaptic buttons of efferent auditory fibers, within the developing and adult auditory receptor. The detection of Syp in aged cochleae could provide relevant information about synaptic changes and receptor degeneration process observed in old animals. This paper focuses on aging linked changes related to the presence of Syp in cochleae of C57BL/6J mice (from 1 to 24 months old). Results showed that during the first months of age, no significant changes were observed in the Syp distribution under the basal pole of inner (IHCs) neither the outer (OHCs) hair cells. At six months of age, a significant decrease of Syp immunocytochemical detection appeared in fibers under the most external row of OHCs, but restricted to the cochlear basal coil. Only a very scarce reduction of Syp was noted under the IHC and the other OHC rows, also at the basal coil. From mice 9 months old on, a progressive decrease of the presence of Syp was found under IHC and all OHC rows starting at the basal coil and reaching the apical coil in the oldest mice. All these data could indicate that the cochlea aging process early affects to presynaptic membrane proteins of efferent endings fibers. This early alteration of cochleae efferent synapses could be involved in the whole degeneration of the Cortis organ.

The effects of adiponectin and leptin on human endothelial cell proliferation: a live-cell study.

The effect of adiponectin and leptin on the proliferation of the human microvascular endothelial cell line (HMEC-1) was studied in the absence or presence of fetal bovine serum (FBS). The participation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase/Akt (PI-3K/Akt) pathways in this effect were evaluated. We studied the effect of both adipokines on the motility, mitosis, proliferation and cell death processes of HMEC-1 cells using live-cell imaging techniques. Adiponectin but not leptin further increased the proliferative effect induced by FBS on HMEC-1. This effect seems to be the consequence of an increase in the mitotic index in adiponectin-treated cells when compared to untreated ones. The presence of either the mitogen-activated protein kinase (MAPK) inhibitor (PD98059), or PI-3K inhibitor (LY294002), reduced the effect of adiponectin in a dose-dependent manner. Neither adipokine was able to affect HMEC-1 proliferation in FBS-free conditions. Duration of mitosis, cell motility and the cell death process were similar in all conditions. These data suggest that adiponectin and leptin exert different effects on endothelial cell function. Adiponectin was able to potentiate proliferation of HMEC-1. This effect involves the activation of both PI3-K/Akt and ERK/MAPK pathways. However, it seems to exert minimal effects on HMEC-1 function in the case of leptin.

Regional differences in low birth weight in Spain: Biological, demographic and socioeconomic variables

The geographic and demographic dimensions of Spain, in terms of surface and number of inhabitants, and its heterogeneous socioeconomic development offer an adequate opportunity to study the provincial differences in birth weight from 1996 to 2010, focusing on possible factors determining the relative frequency of low birth weight. The study analysed geographic differences with regard to biological, demographic and socioeconomic factors that interfere with the female reproductive pattern. The variables considered here were: birth order, proportion of premature deliveries, mothers age, multiparity, mothers country of origin and professional qualifications. Two periods (1996-2000 and 2006-2010) were compared by means of principal components analysis. An increase in the relative frequency of deliveries weighing less than 2500 g occurred in most of the 52 geographic units studied, differences being significant in 42. Only in five cases was there a non-significant reduction in the proportion of low weight births. The first component after principal component analysis indicated that low birth weight was positively related to maternal age and to multiple deliveries, and negatively to the mothers low professional qualification. The second component related positively to the incidence of premature deliveries and to non-Spanish status and negatively in the case of primiparous mothers. The progressive increase in low birth weight incidence observed in Spain from 1996 onwards has occurred with considerable variation in each province. In part, this diversity can be attributed to the unequal reproductive patterns of immigrant mothers.

Temporal and territorial analysis of multiple deliveries in Spain (1900-2006)

Temporal variations in the frequency of multiple maternities in many Western European countries have been described. However, within a single country, regional differences are observed. Urban industrialized regions and rural agricultural areas have experienced in recent decades a distinct decline in multiple deliveries, which in cases have been related to maternal age and parity changes. Research on multiple deliveries in Spain is scarce and none of the studies go back to the beginning of the 20th century or consider regional variation over an extended period of time. The present paper is a yearly study on multiple deliveries in Spain since 1900 including a geographical analysis. Rather than dealing with recent changes in multi-parity, this paper is concerned with Spains long-term national variation (between 1900 and 2006). The changing pattern of double and triple deliveries was analyzed using data from the Spanish National Statistics Institute (INE). Twinning rates in Spain are low in comparison to those of equivalent periods in other countries, and the minimum rates correspond to the 1980s decade. Results were interpreted by taking into account the influence of age at maternity and reproductive variation up to 1990. A good fit between observed and predicted rates was obtained after the application of models, which besides maternal age and parity, include their interaction. Regarding territorial variability, the values corresponding to southern, northern and insular Spanish provinces are consistent with an earlier reduction of the crude birth rate in the north-east regions and latter in the southern regions and the Canary Islands.