Increased potential of a cationic liposome-based delivery system:enhancing stability and sustained immunological activity in pre-clinical development

The combination of dimethyl dioctadecyl ammonium bromide (DDA) and the synthetic cord factor trehalose dibehenate (TDB) with Ag85B-ESAT-6 (H1 fusion protein) has been found to promote strong protective immune responses against Mycobacterium tuberculosis. The development of a vaccine formulation that is able to facilitate the requirements of sterility, stability and generation of a vaccine product with acceptable composition, shelf-life and safety profile may necessitate selected alterations in vaccine formulation. This study describes the implementation of a sterilisation protocol and the use of selected lyoprotective agents in order to fulfil these requirements. Concomitantly, close analysis of any alteration in physico-chemical characteristics and parameters of immunogenicity have been examined for this promising DDA liposome-based tuberculosis vaccine. The study addresses the extensive guidelines on parameters for non-clinical assessment, suitable for liposomal vaccines and other vaccine delivery systems issued by the World Health Organisation (WHO) and the European Medicines Agency (EMEA). Physical and chemical stability was observed following alteration in formulations to include novel cryoprotectants and radiation sterilisation. Immunogenicity was maintained following these alterations and even improved by modification with lysine as the cryoprotective agent for sterilised formulations. Taken together, these results outline the successful alteration to a liposomal vaccine, representing improved formulations by rational modification, whilst maintaining biological activity.

Impaired sustained attention and executive dysfunction:bipolar disorder versus depression-specific markers of affective disorders

Objective - To identify neurocognitive measures that could be used as objective markers of bipolar disorder. Methods - We examined executive function, sustained attention and short-term memory as neurocognitive domains in 18 participants with bipolar disorder in euthymic state (Beuth), 14 in depressed state (Bdep), 20 with unipolar depression (Udep) and 28 healthy control participants (HC). We conducted four-group comparisons followed by relevant post hoc analyses. Results - Udep and Bdep, but not Beuth showed impaired executive function (p = 0.045 and p = 0.046, respectively). Both Bdep and Beuth, but not Udep, showed impaired sustained attention (p = 0.001 and p = 0.045, respectively). The four groups did not differ significantly on short-term memory. Impaired sustained attention and executive dysfunction were not associated with depression severity, duration of illness and age of illness onset. Only a small number of abnormal neurocognitive measures were associated with medication in Bdep and Beuth. Conclusion - Impaired sustained attention appears specific to bipolar disorder and present in both Beuth and Bdep; it may represent an objective marker of bipolar disorder. Executive dysfunction by contrast, appears to be present in Udep and Bdep and likely represents a marker of depression.

Successful and sustained leadership: A case study of a Jesuit high school president

Fr. Marcelino Garc��a, S.J. has been the president of Belen Jesuit Preparatory School for 25 years. The longevity and success of his tenure is an exemplary case of effective leadership and provided significant insight into what constitutes effective school leadership. The target population for this case study consisted of the school���s 7 administrators, 90 faculty members, 10 English-speaking staff members, and 3 key informants. Data were collected using Bolman and Deal���s (1997) Leadership Orientation Survey along with the Jesuit Secondary Education Administration���s (1994) Administrative Leadership Profile Survey (ALPS). Data collected from the surveys were analyzed using the SPSS, version 10. The study also included data collected from focus interviews with Fr. Garc��a and six other significant members of the school community. The interviews were approximately 1-hour individual interviews that employed a semi-structured guide. A concurrent triangulation method was used that directly compared the results from these data collection methods. This was done by looking at the data as a whole and in parts. The parts were internal (faculty, administrators, and staff) and external (parents, alumni, and the superior of the Jesuit community) sectors. The comparison of the findings was then examined in terms of each research question. Analysis of the data revealed that while Fr. Garc��a���s predominant leadership style reflected the typical Bolman and Deal characteristics associated with the political frame, his leadership demonstrates access to all four frames. Research has found a correlation between multiple frame use and successful leadership. Relatedly, Fr. Garc��a���s capacity to approach his administration from various perspectives is indicative of success. In addition, from the perspective of Jesuit education, an analysis of Fr. Garc��a���s leadership indicated recurring themes that contributed to the school���s organizational health. The results of this study provide an extensive analysis of the administration of a unique leader. An analysis of Fr. Garc��a���s leadership style from two perspectives gives fresh insight into sustained and successful leadership.

Occupational contact urticaria: lessons from the French National Network for Occupational Disease Vigilance and Prevention (RNV3P)

International audience

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One of the most important functions in the individual development is the interaction and integration of each sensory input. There exist two competing theories, i.e. the deficiency theory and the compensatory theory, regarding the origin and nature of changes in visual functions observed after auditory deprivation. The deficiency theory proposed that integrative processes are essential for normal development. In contrast, the compensatory theory stated that the loss of one sense may be met by a greater reliance upon, therefore an enhancement of the remaining senses. Given that hearing impaired children���s learning depends primarily on visual information, it is important to recognize the differences of visual attention between them and their hearing age-mates. Differences among age groups could exist in either selectivity or sustained attention. Study 1 and study 2 explored the selective and sustained attention development of hearing impaired and hearing students with average cognitive ability, aged from 7 years to college students. The analysis and discussion of the results are based on the visual attention development as well as deficiency theory and compensatory theory. According to the results of the study 1 and study 2, the spatial distribution and controlling of the visual attention between hearing impaired and hearing students were also investigated in the study 3 and study 4. The present work showed that: Firstly, both hearing impaired and hearing participants had the similar developmental trajectory of the sustained attention. The ability of children���s sustained attention appeared to improve with age, and in adolescence it reached the peak. The hearing impaired participants had the comparable sustained attention skills to the matched hearing ones. Besides, the results of the hearing impaired participants showed that they could maintain their attention and vigilance on the current task over the observation period. Secondly, group differences of visual attention development were found between hearing impaired and hearing participants. In the childhood, the visual attention developmental speed of the hearing impaired children was slower than that of the hearing ones. The selective attention skill of the hearing impaired were not comparable to the hearing ones, however, their selective skill improved with age, so in the adulthood, hearing impaired students showed the slight advantage in the selective attention skill over the hearing ones. Thirdly, hearing impaired and hearing participants showed the similar spatial distribution in the attention resources. In the low perceptual load condition, both participants were suffered great interference of the distrator at the fixation. In contrast, in the high perceptual load condition, hearing impaired adults were suffered more interference of the peripheral distractor, which suggested that they distributed more attention resources to the peripheral field when faced difficult tasks. Fourthly, both groups showed similar processing in the visual attention tasks. That is, they both searched the target with only the color feature in a parallel way, but in a serial way while processing orientation feature and the features with the combination of the color and orientation. Furthermore, the results indicated that two groups show similar ways in the attention controlling. In summary, the present study showed that visual attention development was dependent upon the integration of multimodal sensory information. Because of the interaction and integration of the input from various sensory, it has a negative impact on the intact sensory at the early stage of one sensory loss, however, it can better the functions of other intact sensory gradually with development and practice.

Absence of the 7-repeat variant of the DRD4 VNTR is associated with drifting sustained attention in children with ADHD but not in controls

Many genetic studies have demonstrated an association between the 7-repeat (7r) allele of a 48-base pair variable number of tandem repeats (VNTR) in exon 3 of the DRD4 gene and the phenotype of attention deficit hyperactivity disorder (ADHD). Previous studies have shown inconsistent associations between the 7r allele and neurocognitive performance in children with ADHD. We investigated the performance of 128 children with and without ADHD on the Fixed and Random versions of the Sustained Attention to Response Task (SART). We employed timeseries analyses of reaction-time data to allow a fine-grained analysis of reaction time variability, a candidate endophenotype for ADHD. Children were grouped into either the 7r-present group (possessing at least one copy of the 7r allele) or the 7r-absent group. The ADHD group made significantly more commission errors and was significantly more variable in RT in terms of fast moment-to-moment variability than the control group, but no effect of genotype was found on these measures. Children with ADHD without the 7r allele made significantly more omission errors, were significantly more variable in the slow frequency domain and showed less sensitivity to the signal (d') than those children with ADHD the 7r and control children with or without the 7r. These results highlight the utility of time-series analyses of reaction time data for delineating the neuropsychological deficits associated with ADHD and the DRD4 VNTR. Absence of the 7-repeat allele in children with ADHD is associated with a neurocognitive profile of drifting sustained attention that gives rise to variable and inconsistent performance. (c) 2008 Wiley-Liss, Inc.

Evidence for a cognitive control network for goal-directed attention in simple sustained attention

The deterioration of performance over time is characteristic for sustained attention tasks. This so-called "performance decrement" is measured by the increase of reaction time (RT) over time. Some behavioural and neurobiological mechanisms of this phenomenon are not yet fully understood. Behaviourally, we examined the increase of RT over time and the inter-individual differences of this performance decrement. On the neurophysiological level, we investigated the task-relevant brain areas where neural activity was modulated by RT and searched for brain areas involved in good performance (i.e. participants with no or moderate performance decrement) as compared to poor performance (i.e. participants with a steep performance decrement). For this purpose, 20 healthy, young subjects performed a carefully designed task for simple sustained attention, namely a low-demanding version of the Rapid Visual Information Processing task. We employed a rapid event-related functional magnetic resonance imaging (fMRI) design. The behavioural results showed a significant increase of RT over time in the whole group, and also revealed that some participants were not as prone to the performance decrement as others. The latter was statistically significant comparing good versus poor performers. Moreover, high BOLD-responses were linked to longer RTs in a task-relevant bilateral fronto-cingulate-insular-parietal network. Among these regions, good performance was associated with significantly higher RT-BOLD correlations in the pre-supplementary motor area (pre-SMA). We concluded that the task-relevant bilateral fronto-cingulate-insular-parietal network was a cognitive control network responsible for goal-directed attention. The pre-SMA in particular might be associated with the performance decrement insofar that good performers could sustain activity in this brain region in order to monitor performance declines and adjust behavioural output.

Local and global attention are mapped retinotopically in human occipital cortex

Clinical evidence suggests that control mechanisms for local and global attention are lateralized in the temporal���parietal cortex. However, in the human occipital (visual) cortex, the evidence for lateralized local/global attention is controversial. To clarify this matter, we used functional MRI to map activity in the human occipital cortex, during local and global attention, with sustained visual fixation. Data were analyzed in a flattened cortical format, relative to maps of retinotopy and spatial frequency peak tuning. Neither local nor global attention was lateralized in the occipital cortex. Instead, local attention and global attention appear to be special cases of visual spatial attention, which are mapped consistently with the maps of retinotopy and spatial frequency tuning, in multiple visual cortical areas.

Interval timing in children:effects of auditory and visual pacing stimuli and relationships with reading and attention variables

Motor timing tasks have been employed in studies of neurodevelopmental disorders such as developmental dyslexia and ADHD, where they provide an index of temporal processing ability. Investigations of these disorders have used different stimulus parameters within the motor timing tasks which are likely to affect performance measures. Here we assessed the effect of auditory and visual pacing stimuli on synchronised motor timing performance and its relationship with cognitive and behavioural predictors that are commonly used in the diagnosis of these highly prevalent developmental disorders. Twenty- one children (mean age 9.6 years) completed a finger tapping task in two stimulus conditions, together with additional psychometric measures. As anticipated, synchronisation to the beat (ISI 329 ms) was less accurate in the visually paced condition. Decomposition of timing variance indicated that this effect resulted from differences in the way that visual and auditory paced tasks are processed by central timekeeping and associated peripheral implementation systems. The ability to utilise an efficient processing strategy on the visual task correlated with both reading and sustained attention skills. Dissociations between these patterns of relationship across task modality suggest that not all timing tasks are equivalent.

Metacognition and executive functioning in Elementary School

This study analyzes differences in metacognitive skills and executive functioning between two groups of students (10-12 years) with different levels of metacognitive knowledge (high n = 50, low n = 64). Groups were established based on students' score on a test of knowledge of strategy use. Metacognitive skills were assessed by means of self-report. Students reported the frequency with which they applied these strategies during the phases of planning, execution, and evaluation of learning. Information about student executive functioning was provided by families and teachers, who completed two parallel forms of a behavior rating scale. The results indicated that: a) the group with high levels of metacognitive knowledge reported using their metacognitive skills more frequently than their peers in the other group. These differences were statistically significant in the phases of planning and execution; b) both family and teachers informed of better levels of executive functioning in the students with high metacognitive knowledge. Statistically significant differences were found in planning, functional memory, focus, and sustained attention. These results show the existence of an association between different levels of metacognitive knowledge, and differences in metacognitive skills and executive functions, and suggest the need to emphasize this set of variables in order to encourage students to acquire increasing levels of control over their learning process.

The Role of Fixation and Visual Attention in Object Recognition

This research project is a study of the role of fixation and visual attention in object recognition. In this project, we build an active vision system which can recognize a target object in a cluttered scene efficiently and reliably. Our system integrates visual cues like color and stereo to perform figure/ground separation, yielding candidate regions on which to focus attention. Within each image region, we use stereo to extract features that lie within a narrow disparity range about the fixation position. These selected features are then used as input to an alignment-style recognition system. We show that visual attention and fixation significantly reduce the complexity and the false identifications in model-based recognition using Alignment methods. We also demonstrate that stereo can be used effectively as a figure/ground separator without the need for accurate camera calibration.

View-Invariant Object Category Learning, Recognition, and Search: How Spatial and Object Attention Are Coordinated Using Surface-Based Attentional Shrouds

Air Force Office of Scientific Research (F49620-01-1-0397); National Science Foundation (SBE-0354378); Office of Naval Research (N00014-01-1-0624)

Neural Dynamics of Motion Perception, Recognition Learning, and Spatial Attention

Advanced Research Projects Agency (ONR N00014-92-J-4015); National Science Foundation (IRI-90-24877); Office of Naval Research (N00014-91-J-4100)

Neural Pattern Recognition With Multi-Scale Pyramidal Coding and Selective Attention

A new neural network architecture for spatial patttern recognition using multi-scale pyramida1 coding is here described. The network has an ARTMAP structure with a new class of ART-module, called Hybrid ART-module, as its front-end processor. Hybrid ART-module, which has processing modules corresponding to each scale channel of multi-scale pyramid, employs channels of finer scales only if it is necesssary to discriminate a pattern from others. This process is effected by serial match tracking. Also the parallel match tracking is used to select the spatial location having most salient feature and limit its attention to that part.

Bimanual aiming and overt attention: one law for two hands

Reaching to interact with an object requires a compromise between the speed of the limb movement and the required end-point accuracy. The time it takes one hand to move to a target in a simple aiming task can be predicted reliably from Fitts' law, which states that movement time is a function of a combined measure of amplitude and accuracy constraints (the index of difficulty, ID). It has been assumed previously that Fitts' law is violated in bimanual aiming movements to targets of unequal ID. We present data from two experiments to show that this assumption is incorrect: if the attention demands of a bimanual aiming task are constant then the movements are well described by a Fitts' law relationship. Movement time therefore depends not only on ID but on other task conditions, which is a basic feature of Fitts' law. In a third experiment we show that eye movements are an important determinant of the attention demands in a bimanual aiming task. The results from the third experiment extend the findings of the first two experiments and show that bimanual aiming often relies on the strategic co-ordination of separate actions into a seamless behaviour. A number of the task specific strategies employed by the adult human nervous system were elucidated in the third experiment. The general strategic pattern observed in the hand trajectories was reflected by the pattern of eye movements recorded during the experiment. The results from all three experiments demonstrate that eye movements must be considered as an important constraint in bimanual aiming tasks.