Case study: auditory brain responses in a minimally verbal child with autism and cerebral palsy

An estimated 30% of individuals with autism spectrum disorders (ASD) remain minimally verbal into late childhood, but research on cognition and brain function in ASD focuses almost exclusively on those with good or only moderately impaired language. Here we present a case study investigating auditory processing of GM, a nonverbal child with ASD and cerebral palsy. At the age of 8 years, GM was tested using magnetoencephalography (MEG) whilst passively listening to speech sounds and complex tones. Where typically developing children and verbal autistic children all demonstrated similar brain responses to speech and nonspeech sounds, GM produced much stronger responses to nonspeech than speech, particularly in the 65–165 ms (M50/M100) time window post-stimulus onset. GM was retested aged 10 years using electroencephalography (EEG) whilst passively listening to pure tone stimuli. Consistent with her MEG response to complex tones, GM showed an unusually early and strong response to pure tones in her EEG responses. The consistency of the MEG and EEG data in this single case study demonstrate both the potential and the feasibility of these methods in the study of minimally verbal children with ASD. Further research is required to determine whether GM's atypical auditory responses are characteristic of other minimally verbal children with ASD or of other individuals with cerebral palsy.

Phosphatidylserine-containing liposomes:modulators of rhinovirus induced inflammatory responses

Background: Human rhinoviral infections are major contributors to the healthcare burden associated with acute exacerbations of asthma. We, and others have recently demonstrated that rhinovirus (RV)-induced inflammatory responses are mediated by multiple signalling mechanisms, such as IL-1/MyD88 (1) and TLR3/RIGI (2). We have also previously published work showing that TLR signalling is effectively inhibited by phosphatidylserine-containing liposomes (SAPS), through the disruption of membrane microdomains (3). Evidence has also suggested that membrane microdomains may influence infections with RV. In this study, we explored the ability of SAPS to modulate responses to the natural viral pathogens, RV-1B and RV-16. Method: The immortalized bronchial epithelial cell line, BEAS-2B or primary bronchial epithelial cells were infected with RV-1B or RV-16 at a TCID50/ml of 19107 for 1 h. Immediately following infection, various concentrations of SAPS were added and changes in cytokine release were measured at 24 h. SAPS remained present throughout. Type I and III interferon (IFN) expression and rates of viral replication were measured by quantitative PCR. Virus quantification was also performed using a viral CPE assay, and IFN signalling was measured by western blot. Liposome stability was characterised and intracellular trafficking of fluorescently labelled SAPS in BEAS-2B cells was investigated using confocal microscopy. For in vivo studies, female wt Balb/c mice were pre-treated with SAPS for 2 h prior to infection with RV as previously described and changes in BAL cell number, BAL cytokine production and viral replication were quantified (4). Results: Characterisation of SAPS liposomes by mass spectrometry showed no obvious signs of oxidation over the time period tested, and liposome size remained constant. Preliminary confocal studies revealed that SAPS was rapidly internalised within the cell and was found to associate with intracellular compartments such as the early endosome and golgi. Viral infected BEAS-2B cells co-incubated with SAPS, showed notably impaired responses to RV as assessed by release of CXCL8 and CCL5. SAPS also reduced RV-induced IFNb production and STAT-1 phosphorylation, without significantly influencing viral replication rates. Modest increases in viral particle production were only observed at 48 and 72 h time points. Suppression of viral-induced cytokine production was also observed in primary bronchial epithelial cells and pilot in vivo studies showed that SAPS results in reduced KC production at 24 h post viral infection, and this was associated with reduced neutrophil numbers within the BAL fluid. Conclusion: Our data demonstrates a potential means of modulating inflammatory responses induced by human rhinovirus.

The relationship of systemic markers of renal function and vascular function with retinal blood vessel responses

Purpose: To test the hypothesis of a significant relationship between systemic markers of renal and vascular function (processes linked to cardiovascular disease and its development) and retinal microvascular function in diabetes and/or cardiovascular disease.Methods: Ocular microcirculatory function was measured in 116 patients with diabetes and/or cardiovascular disease using static and continuous retinal vessel responses to three cycles of flickering light. Endothelial function was evaluated by von Willebrand factor (vWf), endothelial microparticles and soluble E selectin, renal function by serum creatinine, creatinine clearance and estimated glomerular filtration rate (eGFR). HbA1c was used as a control index.Results: Central retinal vein equivalence and venous maximum dilation to flicker were linked to HbA1c (both p<0.05). Arterial reaction time was linked to serum creatinine (p=0.036) and eGFR (p=0.039), venous reaction time was linked to creatinine clearance (p=0.018). Creatinine clearance and eGFR were linked to arterial maximum dilatation (p<0.001 and p=0.003 respectively) and the dilatation amplitude (p=0.038 and p=0.048 respectively) responses in the third flicker cycle. Of venous responses to the first flicker cycle, HbA1c was linked to the maximum dilation response (p=0.004) and dilatation amplitude (p=0.017), vWf was linked to the maximum constriction response (p=0.016), and creatinine clearance to the baseline diameter fluctuation (p=0.029). In the second flicker cycle, dilatation amplitude was linked to serum creatinine (p=0.022). Conclusions: Several retinal blood vessel responses to flickering light are linked to glycaemia and renal function, but only one index is linked to endothelial function. Renal function must be considered when interpreting retinal vessel responses.

Early spatial vision:a view through two eyes

Simple features such as edges are the building blocks of spatial vision, and so I ask: how arevisual features and their properties (location, blur and contrast) derived from the responses ofspatial filters in early vision; how are these elementary visual signals combined across the twoeyes; and when are they not combined? Our psychophysical evidence from blur-matchingexperiments strongly supports a model in which edges are found at the spatial peaks ofresponse of odd-symmetric receptive fields (gradient operators), and their blur B is givenby the spatial scale of the most active operator. This model can explain some surprisingaspects of blur perception: edges look sharper when they are low contrast, and when theirlength is made shorter. Our experiments on binocular fusion of blurred edges show that singlevision is maintained for disparities up to about 2.5*B, followed by diplopia or suppression ofone edge at larger disparities. Edges of opposite polarity never fuse. Fusion may be served bybinocular combination of monocular gradient operators, but that combination - involvingbinocular summation and interocular suppression - is not completely understood.In particular, linear summation (supported by psychophysical and physiological evidence)predicts that fused edges should look more blurred with increasing disparity (up to 2.5*B),but results surprisingly show that edge blur appears constant across all disparities, whetherfused or diplopic. Finally, when edges of very different blur are shown to the left and righteyes fusion may not occur, but perceived blur is not simply given by the sharper edge, nor bythe higher contrast. Instead, it is the ratio of contrast to blur that matters: the edge with theAbstracts 1237steeper gradient dominates perception. The early stages of binocular spatial vision speak thelanguage of luminance gradients.

Effects of light quantity and quality on early seedling development in the red mangrove Rhizophora mangle L

Seedlings of the red mangrove, Rhizophora mangle L., were grown under light conditions differing in both photosynthetic photon flux density (PPFD) and spectral quality (red:far-red ratio, R:FR). During the first 8 mo of development, parameters of stem, leaf, and root growth were affected by PPFD. Significant responses to lowered R:FR, however, were limited to internode extension. The results are moderately indicative of a strategy to persist in shade, but illustrate the complexity of light responses and suggest that precise categorization as shade-tolerant or -intolerant may be unbefitting for this species at this particular stage of development.

A methodology to estimate time varying user responses to travel time and travel time reliability in a road pricing environment

Road pricing has emerged as an effective means of managing road traffic demand while simultaneously raising additional revenues to transportation agencies. Research on the factors that govern travel decisions has shown that user preferences may be a function of the demographic characteristics of the individuals and the perceived trip attributes. However, it is not clear what are the actual trip attributes considered in the travel decision- making process, how these attributes are perceived by travelers, and how the set of trip attributes change as a function of the time of the day or from day to day. In this study, operational Intelligent Transportation Systems (ITS) archives are mined and the aggregated preferences for a priced system are extracted at a fine time aggregation level for an extended number of days. The resulting information is related to corresponding time-varying trip attributes such as travel time, travel time reliability, charged toll, and other parameters. The time-varying user preferences and trip attributes are linked together by means of a binary choice model (Logit) with a linear utility function on trip attributes. The trip attributes weights in the utility function are then dynamically estimated for each time of day by means of an adaptive, limited-memory discrete Kalman filter (ALMF). The relationship between traveler choices and travel time is assessed using different rules to capture the logic that best represents the traveler perception and the effect of the real-time information on the observed preferences. The impact of travel time reliability on traveler choices is investigated considering its multiple definitions. It can be concluded based on the results that using the ALMF algorithm allows a robust estimation of time-varying weights in the utility function at fine time aggregation levels. The high correlations among the trip attributes severely constrain the simultaneous estimation of their weights in the utility function. Despite the data limitations, it is found that, the ALMF algorithm can provide stable estimates of the choice parameters for some periods of the day. Finally, it is found that the daily variation of the user sensitivities for different periods of the day resembles a well-defined normal distribution.

Early career special education teachers' perceptions of school site induction support

Research highlights teacher attrition as one of the biggest challenges facing public schools and their attempts to provide a quality teacher for every student (Ingersoll & Smith, 2003). The teacher shortage is particularly daunting in special education where teachers are over twice as likely to leave the field. The first few years of teaching are the most critical in determining whether or not a beginning teacher will stay in the teaching profession (Whitaker, 2000). ^ A mixed-methods sequential explanatory design was utilized to examine research questions focused on the components of induction support that early career teachers received at their school site, including what they considered most valuable to their long-term retention in the classroom and their development as a quality teacher. Eighty seven early career special education teachers were surveyed during the first phase of the study and six participants were interviewed during the second phase. ^ Data analysis of the Likert-scale survey used in the study revealed that the majority of the respondents received at least 21 of the 25 listed induction components. Moreover, early career special education teachers indicated that they valued all 25 induction components. In addition, findings revealed that over two thirds of the respondents indicated a desire to remain a special education teacher. Overall, early career special education teachers felt confident in their abilities to teach students with disabilities; however, nearly half of the respondents did not feel satisfied with the induction they received. Independent t-tests showed a statistically significant difference between teachers who indicated a desire to remain in special education and those that did not on the level of satisfaction with their induction experience. ^ The six interviews provided elaboration and clarification of the survey responses. The participants expressed their passion for the art of teaching, their dedication to students with disabilities, and their frustration with being a beginning teacher. Furthermore, it was reported that the overall school culture was not very supportive. Participants offered relevant ideas for additional or alternate induction components that would be more effective.^

Survival and growth responses of eight Everglades tree species along an experimental hydrological gradient on two tree island types

Questions: How are the early survival and growth of seedlings of Everglades tree species planted in an experimental setting on artificial tree islands affected by hydrology and substrate type? What are the implications of these responses for broader tree island restoration efforts? Location: Loxahatchee Impoundment Landscape Assessment (LILA), Boynton Beach, Florida, USA. Methods: An experiment was designed to test hydrological and substrate effects on seedling growth and survivorship. Two islands – a peat and a limestone-core island representing two major types found in the Everglades – were constructed in four macrocosms. A mixture of eight tree species was planted on each island in March of 2006 and 2007. Survival and height growth of seedlings planted in 2006 were assessed periodically during the next two and a half years. Results: Survival and growth improved with increasing elevation on both tree island substrate types. Seedlings' survival and growth responses along a moisture gradient matched species distributions along natural hydrological gradients in the Everglades. The effect of substrate on seedling performance showed higher survival of most species on the limestone tree islands, and faster growth on their peat-based counterparts. Conclusions: The present results could have profound implications for restoration of forests on existing landforms and artificial creation of tree islands. Knowledge of species tolerance to flooding and responses to different edaphic conditions present in wetlands is important in selecting suitable species to plant on restored tree islands

Adaptive software fault prediction approach using object-oriented metrics

As users continually request additional functionality, software systems will continue to grow in their complexity, as well as in their susceptibility to failures. Particularly for sensitive systems requiring higher levels of reliability, faulty system modules may increase development and maintenance cost. Hence, identifying them early would support the development of reliable systems through improved scheduling and quality control. Research effort to predict software modules likely to contain faults, as a consequence, has been substantial. Although a wide range of fault prediction models have been proposed, we remain far from having reliable tools that can be widely applied to real industrial systems. For projects with known fault histories, numerous research studies show that statistical models can provide reasonable estimates at predicting faulty modules using software metrics. However, as context-specific metrics differ from project to project, the task of predicting across projects is difficult to achieve. Prediction models obtained from one project experience are ineffective in their ability to predict fault-prone modules when applied to other projects. Hence, taking full benefit of the existing work in software development community has been substantially limited. As a step towards solving this problem, in this dissertation we propose a fault prediction approach that exploits existing prediction models, adapting them to improve their ability to predict faulty system modules across different software projects.

An investigation of parents' and children's beliefs of early literacy acquisition from a cross -cultural perspective

It has been reported that the cultural-historical experiences of ethnic group members can play a role in the literacy beliefs of those members. Socioeconomic conditions can also influence the belief system of the groups' constituents. This study investigated parents' and children's beliefs pertaining to early literacy acquisition as related to the ethnicity and socioeconomic status (SES) of the participants. The objectives were to determine (a) the differential patterns regarding emergent literacy and traditional skills approaches as they interact with ethnicity and SES and (b) the correspondence between parents and children's beliefs about literacy acquisition. ^ The study was conducted with 152 parents (38 low-income Hispanic, 38 middle-income Hispanic, 38 low-income African-American, and 38 middle-income African-American) and 36 of their 3-, 4-, or 5-year-old children (18 male and 18 female). ^ The parents were asked to check those items with which they agreed on a survey that consisted of an equal number of items from the traditional skills-based and emergent literacy orientations. These responses were used to determine the differences and interaction by ethnicity and SES. The children responded to open-ended questions related to the instruction of reading and writing skills. The parents' responses and children's answers were compared to ascertain the matching parent-child dyads by ethnicity and SES. ^ An item analysis was conducted to strengthen the internal reliability consistency coefficient of the traditional skills-based and emergent literacy scales as measured by the Cronbach Alpha. ^ A two-way multivariate analysis of variance (MANOVA) revealed a significant difference in traditional skill-based beliefs for the low-income African-American and Hispanic parents. There were no significant findings for the parents' traditional skill based or emergent literacy beliefs based on ethnicity, for the interaction between ethnicity and SES, or for the relationship between parents' and children's literacy beliefs by ethnicity and SES. ^ It can be concluded that low-income African-American and Hispanic parents believe in the traditional skills approach, indicating that these parents find it necessary for children to have sufficient school readiness skills prior to learning to read or write. In addition, the parent and child dyads had a strong tendency toward emergent literacy beliefs. ^

The role of *language in early childhood mathematics

Math literacy is imperative to succeed in society. Experience is key for acquiring math literacy. A preschooler's world is full of mathematical experiences. Children are continually counting, sorting and comparing as they play. As children are engaged in these activities they are using language as a tool to express their mathematical thinking. If teachers are aware of these teachable moments and help children bridge their daily experiences to mathematical concepts, math literacy may be enhanced. This study described the interactions between teachers and preschoolers, determining the extent to which teachers scaffold children's everyday language into expressions of mathematical concepts. Of primary concern were the teachers' responsive interactions to children's expressions of an implicit mathematical utterance made while engaged in block play. The parallel mixed methods research design consisted of two strands. Strand 1 of the study focused on preschoolers' use of everyday language and the teachers' responses after a child made a mathematical utterance. Twelve teachers and 60 students were observed and videotaped while engaged in block play. Each teacher worked with five children for 20 minutes, yielding 240 minutes of observation. Interaction analysis was used to deductively analyze the recorded observations and field notes. Using a priori codes for the five mathematical concepts, it was found children produced 2,831 mathematical utterances. Teachers ignored 60% of these utterances and responded to, but did not mediate 30% of them. Only 10% of the mathematical utterances were mediated to a mathematical concept. Strand 2 focused on the teacher's view of the role of language in early childhood mathematics. The 12 teachers who had been observed as part of the first strand of the study were interviewed. Based on a thematic analysis of these interviews three themes emerged: (a) the importance of a child's environment, (b) the importance of an education in society, and (c) the role of math in early childhood. Finally, based on a meta-inference of both strands, three themes emerged: (a) teacher conception of math, (b) teacher practice, and (c) teacher sensitivity. Implications based on the findings involve policy, curriculum, and professional development.

Data compilation on the biological response to ocean acidification: environmental and experimental context of data sets and related literature

The exponential growth of studies on the biological response to ocean acidification over the last few decades has generated a large amount of data. To facilitate data comparison, a data compilation hosted at the data publisher PANGAEA was initiated in 2008 and is updated on a regular basis (doi:10.1594/PANGAEA.149999). By January 2015, a total of 581 data sets (over 4 000 000 data points) from 539 papers had been archived. Here we present the developments of this data compilation five years since its first description by Nisumaa et al. (2010). Most of study sites from which data archived are still in the Northern Hemisphere and the number of archived data from studies from the Southern Hemisphere and polar oceans are still relatively low. Data from 60 studies that investigated the response of a mix of organisms or natural communities were all added after 2010, indicating a welcomed shift from the study of individual organisms to communities and ecosystems. The initial imbalance of considerably more data archived on calcification and primary production than on other processes has improved. There is also a clear tendency towards more data archived from multifactorial studies after 2010. For easier and more effective access to ocean acidification data, the ocean acidification community is strongly encouraged to contribute to the data archiving effort, and help develop standard vocabularies describing the variables and define best practices for archiving ocean acidification data.

Effects of ocean acidification on embryonic respiration and development of a temperate wrasse living along a natural CO2 gradient

Volcanic CO2 seeps provide opportunities to investigate the effects of ocean acidification on organisms in the wild. To understand the influence of increasing CO2 concentrations on the metabolic rate (oxygen consumption) and the development of ocellated wrasse early life stages, we ran two field experiments, collecting embryos from nesting sites with different partial pressures of CO2 [pCO2; ambient (400 µatm) and high (800-1000 µatm)] and reciprocally transplanting embryos from ambient- to high-CO2 sites for 30 h. Ocellated wrasse offspring brooded in different CO2 conditions had similar responses, but after transplanting portions of nests to the high-CO2 site, embryos from parents that spawned in ambient conditions had higher metabolic rates. Although metabolic phenotypic plasticity may show a positive response to high CO2, it often comes at a cost, in this case as a smaller size at hatching. This can have adverse effects because smaller larvae often exhibit a lower survival in the wild. However, the adverse effects of increased CO2 on metabolism and development did not occur when embryos from the high-CO2 nesting site were exposed to ambient conditions, suggesting that offspring from the high-CO2 nesting site could be resilient to a wider range of pCO2 values than those belonging to the site with present-day pCO2 levels. Our study identifies a crucial need to increase the number of studies dealing with these processes under global change trajectories and to expand these to naturally high-CO2 environments, in order to assess further the adaptive plasticity mechanism that encompasses non-genetic inheritance (epigenetics) through parental exposure and other downstream consequences, such as survival of larvae.

Cyclostratigraphy and eccentricity tuning of the early Oligocene through early Miocene record from Walvis Ridge

Few astronomically calibrated high-resolution (<=5 kyr) climate records exist that span the Oligocene-Miocene time interval. Notably, available proxy records show responses varying in amplitude at frequencies related to astronomical forcing, and the main pacemakers of global change on astronomical time-scales remain debated. Here we present newly generated X-ray fluorescence core scanning and benthic foraminiferal stable oxygen and carbon isotope records from Ocean Drilling Program Site 1264 (Walvis Ridge, southeastern Atlantic Ocean). Complemented by data from nearby Site 1265, the Site 1264 benthic stable isotope records span a continuous ~13-Myr interval of the Oligo-Miocene (30.1-17.1 Ma) at high resolution (~3.0 kyr). Spectral analyses in the stratigraphic depth domain indicate that the largest amplitude variability of all proxy records is associated with periods of ~3.4 m and ~0.9 m, which correspond to 405- and ~110-kyr eccentricity, using a magnetobiostratigraphic age model. Maxima in CaCO3 content, d18O and d13C are interpreted to coincide with ~110 kyr eccentricity minima. The strong expression of these cycles in combination with the weakness of the precession- and obliquity-related signals allow construction of an astronomical age model that is solely based on tuning the CaCO3 content to the nominal (La2011_ecc3L) eccentricity solution. Very long-period eccentricity maxima (~2.4-Myr) are marked by recurrent episodes of high-amplitude ~110-kyr d18O cycles at Walvis Ridge, indicating greater sensitivity of the climate/cryosphere system to short eccentricity modulation of climatic precession. In contrast, the responses of the global (high-latitude) climate system, cryosphere, and carbon cycle to the 405-kyr cycle, as expressed in benthic d18O and especially d13C signals, are more pronounced during ~2.4-Myr minima. The relationship between the recurrent episodes of high-amplitude ~110-kyr d18O cycles and the ~1.2-Myr amplitude modulation of obliquity is not consistent through the Oligo-Miocene. Identification of these recurrent episodes at Walvis Ridge, and their pacing by the ~2.4-Myr eccentricity cycle, revises the current understanding of the main climate events of the Oligo-Miocene.

Development of Swept Source Optical Coherence Tomography and Adaptive Optics Scanning Laser Ophthalmoscopy: Improved Imaging Speed and Handheld Applications

Optical coherence tomography (OCT) is a noninvasive three-dimensional interferometric imaging technique capable of achieving micrometer scale resolution. It is now a standard of care in ophthalmology, where it is used to improve the accuracy of early diagnosis, to better understand the source of pathophysiology, and to monitor disease progression and response to therapy. In particular, retinal imaging has been the most prevalent clinical application of OCT, but researchers and companies alike are developing OCT systems for cardiology, dermatology, dentistry, and many other medical and industrial applications.

Adaptive optics (AO) is a technique used to reduce monochromatic aberrations in optical instruments. It is used in astronomical telescopes, laser communications, high-power lasers, retinal imaging, optical fabrication and microscopy to improve system performance. Scanning laser ophthalmoscopy (SLO) is a noninvasive confocal imaging technique that produces high contrast two-dimensional retinal images. AO is combined with SLO (AOSLO) to compensate for the wavefront distortions caused by the optics of the eye, providing the ability to visualize the living retina with cellular resolution. AOSLO has shown great promise to advance the understanding of the etiology of retinal diseases on a cellular level.

Broadly, we endeavor to enhance the vision outcome of ophthalmic patients through improved diagnostics and personalized therapy. Toward this end, the objective of the work presented herein was the development of advanced techniques for increasing the imaging speed, reducing the form factor, and broadening the versatility of OCT and AOSLO. Despite our focus on applications in ophthalmology, the techniques developed could be applied to other medical and industrial applications. In this dissertation, a technique to quadruple the imaging speed of OCT was developed. This technique was demonstrated by imaging the retinas of healthy human subjects. A handheld, dual depth OCT system was developed. This system enabled sequential imaging of the anterior segment and retina of human eyes. Finally, handheld SLO/OCT systems were developed, culminating in the design of a handheld AOSLO system. This system has the potential to provide cellular level imaging of the human retina, resolving even the most densely packed foveal cones.