Stimulus Variability Affects the Amplitude of the Auditory Steady-State Response

In this study we investigate whether stimulus variability affects the auditory steady-state response (ASSR). We present cosinusoidal AM pulses as stimuli where we are able to manipulate waveform shape independently of the fixed repetition rate of 4 Hz. We either present sounds in which the waveform shape, the pulse-width, is fixed throughout the presentation or where it varies pseudo-randomly. Importantly, the average spectra of all the fixed-width AM stimuli are equal to the spectra of the mixed-width AM. Our null hypothesis is that the average ASSR to the fixed-width AM will not be significantly different from the ASSR to the mixed-width AM. In a region of interest beamformer analysis of MEG data, we compare the 4 Hz component of the ASSR to the mixed-width AM with the 4 Hz component of the ASSR to the pooled fixed-width AM. We find that at the group level, there is a significantly greater response to the variable mixed-width AM at the medial boundary of the Middle and Superior Temporal Gyri. Hence, we find that adding variability into AM stimuli increases the amplitude of the ASSR. This observation is important, as it provides evidence that analysis of the modulation waveform shape is an integral part of AM processing. Therefore, standard steady-state studies in audition, using sinusoidal AM, may not be sensitive to a key feature of acoustic processing

Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I

Development of childhood asthma prediction models using machine learning approaches

Background: Respiratory symptoms are common in early life and often transient. It is difficult to identify in which children these will persist and result in asthma. Machine learning (ML) approaches have the potential for better predictive performance and generalisability over existing childhood asthma prediction models. This study applied ML approaches to predict school-age asthma (age 10) in early life (Childhood Asthma Prediction in Early life, CAPE model) and at preschool age (Childhood Asthma Prediction at Preschool age, CAPP model). Methods: Clinical and environmental exposure data was collected from children enrolled in the Isle of Wight Birth Cohort (N = 1368, ∼15% asthma prevalence). Recursive Feature Elimination (RFE) identified an optimal subset of features predictive of school-age asthma for each model. Seven state-of-the-art ML classification algorithms were used to develop prognostic models. Training was performed by applying fivefold cross-validation, imputation, and resampling. Predictive performance was evaluated on the test set. Models were further externally validated in the Manchester Asthma and Allergy Study (MAAS) cohort. Results: RFE identified eight and twelve predictors for the CAPE and CAPP models, respectively. Support Vector Machine (SVM) algorithms provided the best performance for both the CAPE (area under the receiver operating characteristic curve, AUC = 0.71) and CAPP (AUC = 0.82) models. Both models demonstrated good generalisability in MAAS (CAPE 8-year = 0.71, 11-year = 0.71, CAPP 8-year = 0.83, 11-year = 0.79) and excellent sensitivity to predict a subgroup of persistent wheezers. Conclusion: Using ML approaches improved upon the predictive performance of existing regression-based models, with good generalisability and ability to rule in asthma and predict persistent wheeze.</p

The structure and evolution of a forming galaxy cluster at z = 1.62

We present a comprehensive picture of the Cl 0218.3−0510 protocluster at z = 1.623 across 10 comoving Mpc. Using filters that tightly bracket the Balmer and 4000 Å breaks of the protocluster galaxies we obtain precise photometric redshifts resulting in a protocluster galaxy sample that is 89 ± 5 per cent complete and has a contamination of only 12 ± 5 per cent. Both star-forming and quiescent protocluster galaxies are located, which allows us to map the structure of the forming cluster for the first time. The protocluster contains six galaxy groups, the largest of which is the nascent cluster. Only a small minority of the protocluster galaxies are in the nascent cluster (11 per cent) or in the other galaxy groups (22 per cent), as most protocluster galaxies reside between the groups. Unobscured star-forming galaxies predominantly reside between the protocluster’s groups, whereas red galaxies make up a large fraction of the groups’ galactic content, so observing the protocluster through only one of these types of galaxies results in a biased view of the protocluster’s structure. The structure of the protocluster reveals how much mass is available for the future growth of the cluster and we use the Millennium Simulation, scaled to a Planck cosmology, to predict that Cl 0218.3−0510 will evolve into a 2.7+3.9 −1.7 × 1014M cluster by the present day

Paediatric radiology seen from Africa. Part I: providing diagnostic imaging to a young population

Article approval pendingPaediatric radiology requires dedicated equipment, specific precautions related to ionising radiation, and specialist knowledge. Developing countries face difficulties in providing adequate imaging services for children. In many African countries, children represent an increasing proportion of the population, and additional challenges follow from extreme living conditions, poverty, lack of parental care, and exposure to tuberculosis, HIV, pneumonia, diarrhoea and violent trauma. Imaging plays a critical role in the treatment of these children, but is expensive and difficult to provide. The World Health Organisation initiatives, of which the World Health Imaging System for Radiography (WHIS-RAD) unit is one result, needs to expand into other areas such as the provision of maintenance servicing. New initiatives by groups such as Rotary and the World Health Imaging Alliance to install WHIS-RAD units in developing countries and provide digital solutions, need support. Paediatric radiologists are needed to offer their services for reporting, consultation and quality assurance for free by way of teleradiology. Societies for paediatric radiology are needed to focus on providing a volunteer teleradiology reporting group, information on child safety for basic imaging, guidelines for investigations specific to the disease spectrum, and solutions for optimising imaging in children

The thermal emission of the exoplanets WASP-1b and WASP-2b

We present a comparative study of the thermal emission of the transiting exoplanets WASP-1b and WASP-2b using the Spitzer Space Telescope. The two planets have very similar masses but suffer different levels of irradiation and are predicted to fall either side of a sharp transition between planets with and without hot stratospheres. WASP-1b is one of the most highly irradiated planets studied to date. We measure planet/star contrast ratios in all four of the IRAC bands for both planets (3.6-8.0um), and our results indicate the presence of a strong temperature inversion in the atmosphere of WASP-1b, particularly apparent at 8um, and no inversion in WASP-2b. In both cases the measured eclipse depths favor models in which incident energy is not redistributed efficiently from the day side to the night side of the planet. We fit the Spitzer light curves simultaneously with the best available radial velocity curves and transit photometry in order to provide updated measurements of system parameters. We do not find significant eccentricity in the orbit of either planet, suggesting that the inflated radius of WASP-1b is unlikely to be the result of tidal heating. Finally, by plotting ratios of secondary eclipse depths at 8um and 4.5um against irradiation for all available planets, we find evidence for a sharp transition in the emission spectra of hot Jupiters at an irradiation level of 2 x 10^9 erg/s/cm^2. We suggest this transition may be due to the presence of TiO in the upper atmospheres of the most strongly irradiated hot Jupiters.Comment: 10 pages, submitted to Ap

Renormalization of the charged scalar field in curved space

The DeWitt-Schwinger proper time point-splitting procedure is applied to a massive complex scalar field with arbitrary curvature coupling interacting with a classical electromagnetic field in a general curved spacetime. The scalar field current is found to have a linear divergence. The presence of the external background gauge field is found to modify the stress-energy tensor results of Christensen for the neutral scalar field by adding terms of the form $(eF)^2$ to the logarithmic counterterms. These results are shown to be expected from an analysis of the degree of divergence of scalar quantum electrodynamics.Comment: 24 pages REVTe

Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brain

<p>Abstract</p> <p>Background</p> <p>Variations in sortilin-related receptor (SORL1) expression and function have been implicated in Alzheimers Disease (AD). Here, to gain insights into SORL1, we evaluated SORL1 expression and splicing as a function of AD and AD neuropathology, neural gene expression and a candidate single nucleotide polymorphism (SNP).</p> <p>Results</p> <p>To identify SORL1 splice variants, we scanned each of the 46 internal SORL1 exons in human brain RNA samples and readily found SORL1 isoforms that lack exon 2 or exon 19. Quantification in a case-control series of the more abundant isoform lacking exon 2 (delta-2-SORL1), as well as the "full-length" SORL1 (FL-SORL1) isoform containing exon 2 showed that expression of FL-SORL1 was reduced in AD individuals. Moreover, FL-SORL1 was reduced in cognitively intact individuals with significant AD-like neuropathology. In contrast, the expression of the delta-2-SORL1 isoform was similar in AD and non-AD brains. The expression of FL-SORL1 was significantly associated with synaptophysin expression while delta-2-SORL1 was modestly enriched in white matter. Lastly, FL-SORL1 expression was associated with rs661057, a SORL1 intron one SNP that has been associated with AD risk. A linear regression analysis found that rs661057, synaptophysin expression and AD neuropathology were each associated with FL-SORL1 expression.</p> <p>Conclusion</p> <p>These results confirm that FL-SORL1 expression declines in AD and with AD-associated neuropathology, suggest that FL-SORL1 declines in cognitively-intact individuals with AD-associated neuropathology, identify a novel SORL1 splice variant that is expressed similarly in AD and non-AD individuals, and provide evidence that an AD-associated SNP is associated with SORL1 expression. Overall, these results contribute to our understanding of SORL1 expression in the human brain.</p

SCUBA-2 Ultra Deep Imaging EAO Survey (STUDIES). II. Structural Properties and Near-infrared Morphologies of Faint Submillimeter Galaxies

We present structural parameters and morphological properties of faint 450 μm selected submillimeter galaxies (SMGs) from the JCMT Large Program, STUDIES, in the COSMOS-CANDELS region. Their properties are compared to an 850 μm selected and a matched star-forming samples. We investigate stellar structures of 169 faint 450 μm sources (S 450 = 2.8–29.6 mJy; S/N > 4) at z 2 mJy) and more extended than the star-forming galaxies in the same redshift range. For the stellar mass and SFR-matched sample at z sime 1 and z sime 2, the size differences are marginal between faint SMGs and the matched galaxies. Moreover, faint SMGs have similar Sérsic indices and projected axis ratios as star-forming galaxies with the same stellar mass and SFR. Both SMGs and the matched galaxies show high fractions (~70%) of disturbed features at z sime 2, and the fractions depend on the SFRs. These suggest that their star formation activity is related to galaxy merging and the stellar structures of SMGs are similar to those of star-forming galaxies. We show that the depths of submillimeter surveys are approaching the lower luminosity end of star-forming galaxies, allowing us to detect galaxies on the main sequence