Colorimetric and Longitudinal Analysis of Leukocoria in Recreational Photographs of Children with Retinoblastoma

Retinoblastoma is the most common primary intraocular tumor in children. The first sign that is often reported by parents is the appearance of recurrent leukocoria (i.e., “white eye”) in recreational photographs. A quantitative definition or scale of leukocoria – as it appears during recreational photography – has not been established, and the amount of clinical information contained in a leukocoric image (collected by a parent) remains unknown. Moreover, the hypothesis that photographic leukocoria can be a sign of early stage retinoblastoma has not been tested for even a single patient. This study used commercially available software (Adobe Photoshop®) and standard color space conversion algorithms (operable in Microsoft Excel®) to quantify leukocoria in actual “baby pictures” of 9 children with retinoblastoma (that were collected by parents during recreational activities i.e., in nonclinical settings). One particular patient with bilateral retinoblastoma (“Patient Zero”) was photographed >7, 000 times by his parents (who are authors of this study) over three years: from birth, through diagnosis, treatment, and remission. This large set of photographs allowed us to determine the longitudinal and lateral frequency of leukocoria throughout the patient's life. This study establishes: (i) that leukocoria can emerge at a low frequency in early-stage retinoblastoma and increase in frequency during disease progression, but decrease upon disease regression, (ii) that Hue, Saturation and Value (i.e., HSV color space) are suitable metrics for quantifying the intensity of retinoblastoma-linked leukocoria; (iii) that different sets of intraocular retinoblastoma tumors can produce distinct leukocoric reflections; and (iv) the Saturation-Value plane of HSV color space represents a convenient scale for quantifying and classifying pupillary reflections as they appear during recreational photography

Multimodal nested sampling: an efficient and robust alternative to MCMC methods for astronomical data analysis

In performing a Bayesian analysis of astronomical data, two difficult problems often emerge. First, in estimating the parameters of some model for the data, the resulting posterior distribution may be multimodal or exhibit pronounced (curving) degeneracies, which can cause problems for traditional MCMC sampling methods. Second, in selecting between a set of competing models, calculation of the Bayesian evidence for each model is computationally expensive. The nested sampling method introduced by Skilling (2004), has greatly reduced the computational expense of calculating evidences and also produces posterior inferences as a by-product. This method has been applied successfully in cosmological applications by Mukherjee et al. (2006), but their implementation was efficient only for unimodal distributions without pronounced degeneracies. Shaw et al. (2007), recently introduced a clustered nested sampling method which is significantly more efficient in sampling from multimodal posteriors and also determines the expectation and variance of the final evidence from a single run of the algorithm, hence providing a further increase in efficiency. In this paper, we build on the work of Shaw et al. and present three new methods for sampling and evidence evaluation from distributions that may contain multiple modes and significant degeneracies; we also present an even more efficient technique for estimating the uncertainty on the evaluated evidence. These methods lead to a further substantial improvement in sampling efficiency and robustness, and are applied to toy problems to demonstrate the accuracy and economy of the evidence calculation and parameter estimation. Finally, we discuss the use of these methods in performing Bayesian object detection in astronomical datasets.Comment: 14 pages, 11 figures, submitted to MNRAS, some major additions to the previous version in response to the referee's comment

Neutralizing positive charges at the surface of a protein lowers its rate of amide hydrogen exchange without altering its structure or increasing its thermostability

This paper combines two techniques—mass spectrometry and protein charge ladders—to examine the relationship between the surface charge and hydrophobicity of a protein (bovine carbonic anhydrase II; BCA II) and its rate of amide hydrogen-deuterium (H/D) exchange. Mass spectrometric analysis indicated that the sequential acetylation of surface lysine-$\epsilon$-NH$_{3}$$^{+}$ groups—a type of modification that increases the net negative charge and hydrophobicity of the surface of BCA II without affecting its 2° or 3° structure—resulted in a linear increase in the total number of backbone amide hydrogen that are protected from exchange with solvent (2 h, pD 7.4, 15 ºC). Each successive acetylation produced BCA II proteins with one additional hydrogen protected after two hours in deuterated buffer (pD 7.4, 15 ºC). NMR spectroscopy demonstrated that these protected hydrogen atoms were not located on the side chain of the acetylated lysine residues (i.e., lys-$\epsilon$-NHCOCH$_{3}$). The decrease in rate of exchange associated with acetylation paralleled a decrease in thermostability: the most slowly exchanging rungs were the least thermostable (as measured by differential scanning calorimetry). The fact that the rates of H/D exchange were similar for perbutyrated BCA II (e.g., [lys-$\epsilon$-NHCO(CH$_{2}$)$_{2}$CH$_{3}$]$_{18}$) and peracetylated BCA II (e.g., [lys-$\epsilon$-NHCOCH$_{3}$]$_{18}$) suggests that the charge is more important than the hydrophobicity of surface groups in determining the rate of H/D exchange. These kinetic electrostatic effects could complicate the interpretation of experiments in which H/D exchange methods are used to probe the structural effects of non-isoelectric perturbations to proteins (i.e., phosphorylation, acetylation, or the binding of the protein to an oligonucleotide or another charged ligand or protein).Chemistry and Chemical Biolog

Massive Halos in Millennium Gas Simulations: Multivariate Scaling Relations

The joint likelihood of observable cluster signals reflects the astrophysical evolution of the coupled baryonic and dark matter components in massive halos, and its knowledge will enhance cosmological parameter constraints in the coming era of large, multi-wavelength cluster surveys. We present a computational study of intrinsic covariance in cluster properties using halo populations derived from Millennium Gas Simulations (MGS). The MGS are re-simulations of the original 500 Mpc/h Millennium Simulation performed with gas dynamics under two different physical treatments: shock heating driven by gravity only (GO) and a second treatment with cooling and preheating (PH). We examine relationships among structural properties and observable X-ray and Sunyaev-Zel'dovich (SZ) signals for samples of thousands of halos with M_200 > 5 \times 10^{13} Msun/h and z < 2. While the X-ray scaling behavior of PH model halos at low-redshift offers a good match to local clusters, the model exhibits non-standard features testable with larger surveys, including weakly running slopes in hot gas observable--mass relations and ~10% departures from self-similar redshift evolution for 10^14 Msun/h halos at redshift z ~ 1. We find that the form of the joint likelihood of signal pairs is generally well-described by a multivariate, log-normal distribution, especially in the PH case which exhibits less halo substructure than the GO model. At fixed mass and epoch, joint deviations of signal pairs display mainly positive correlations, especially the thermal SZ effect paired with either hot gas fraction (r=0.88/0.69 for PH/GO at z=0) or X-ray temperature (r=0.62/0.83). We discuss halo mass selection by signal pairs, and find a minimum mass scatter of 4% in the \PH model by combining thermal SZ and gas fraction measurements.Comment: 19 pages, 14 figures, submitted to Ap

A single-centre investigator-blinded randomised parallel-group study protocol to investigate the influence of an acclimatisation appointment on children’s behaviour during N2O/O2 sedation as measured by psychological, behavioural and real-time physiological parameters

Aims and objectives To describe a study protocol of a randomised control trial (RCT) assessing the effectiveness, in reducing dental anxiety, of an acclimatising nitrous oxide sedation (N2O) session prior to actual dental treatment with N2O. Materials and methods A single-centre investigator-blinded parallel-group RCT conducted in a postgraduate dental hospital in Dubai, United Arab Emirates (UAE). Anxious children requiring N2O (aged 5–15 years) will be randomly assigned to; a study group: children who will have a preparatory N2O trial experience or; a control group: children who will only have N2O explained to them. Treatment with N2O for both groups will start at the second visit. The following outcomes will be recorded: completion of dental treatment, anxiety scores at baseline and after treatment (using the Modified Child Dental Anxiety Scale faces), behaviour of the child (using Frankl Rating Behaviour Scale) and the acquisition of real-time physiological anxiety-related parameters (using E4® electronic wrist devices). Results The data will be analysed statistically. Discussion There is a paucity of research regarding dental N2O acclimatising appointments. This RCT will supplement existing literature. Conclusions This RCT will report whether prior acclimatising of a child to N2O sedation is effective, or not, in improving dental treatment behaviour

Basal ganglia morphometry and repetitive behavior in young children with autism spectrum disorder

We investigated repetitive and stereotyped behavior (RSB) and its relationship to morphometric measures of the basal ganglia and thalami in 3-4 year old children with autism spectrum disorder (ASD; n=77) and developmental delay without autism (DD; n=34). Children were assessed through clinical evaluation and parent report using RSB-specific scales extracted from the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview, and the Aberrant Behavior Checklist. A subset of children with ASD (n=45), DD (n=14) and a group of children with typical development (TD; n=25) were also assessed by magnetic resonance imaging (MRI). Children with ASD demonstrated elevated RSB across all measures compared to children with DD. Enlargement of the left and right striatum, more specifically the left and right putamen, and left caudate, was observed in the ASD compared to the TD group. However, nuclei were not significantly enlarged after controlling for cerebral volume. The DD group, in comparison to the ASD group, demonstrated smaller thalami and basal ganglia regions even when scaled for cerebral volume, with the exception of the left striatum, left putamen, and right putamen. Elevated RSB, as measured by the ADOS, was associated with decreased volumes in several brain regions: left thalamus, right globus pallidus, left and right putamen, right striatum and a trend for left globus pallidus and left striatum within the ASD group. These results confirm earlier reports that RSB is common early in the clinical course of ASD and, furthermore, demonstrate that such behaviors may be associated with decreased volumes of the basal ganglia and thalamus

Strong lensing in the MareNostrum Universe: biases in the cluster lens population

Strong lensing is one of the most direct probes of the mass distribution in the inner regions of galaxy clusters. It can be used to constrain the density profiles and to measure the mass of the lenses. Moreover, the abundance of strong lensing events can be used to constrain the structure formation and the cosmological parameters through the so-called "arc-statistics" approach. However, several issues related to the usage of strong lensing clusters in cosmological applications are still controversial, leading to the suspect that several biases may affect this very peculiar class of objects. With this study we aim at better understanding the properties of galaxy clusters which can potentially act as strong lenses. We do so by investigating the properties of a large sample of galaxy clusters extracted from the N-body/hydrodynamical simulation MareNostrum Universe. We explore the correlation between the cross section for lensing and many properties of clusters, like the mass, the three-dimensional and projected shapes, their concentrations, the X-ray luminosity and the dynamical activity. We find that the probability of strong alignments between the major axes of the lenses and the line of sight is a growing function of the lensing cross section. In projection, the strong lenses appear rounder within R200, but we find that their cores tend to be more elliptical as the lensing cross section increases. We also find that the cluster concentrations estimated from the projected density profiles tend to be biased high. The X-ray luminosity of strong lensing clusters is higher than that of normal lenses of similar mass and redshift. This is particular significant for the least massive lenses. Finally, we find that the strongest lenses generally exhibit an excess of kinetic energy within the virial radius, indicating that they are more dynamically active than usual clusters.Comment: 22 pages, 18 figures, accepted for publication on A&

The correlation of RNase A enzymatic activity with the changes in the distance between Nepsilon2-His12 and N delta1-His119 upon addition of stabilizing and destabilizing salts.

The effect of stabilizing and destabilizing salts on the catalytic behavior of ribonuclease A (RNase A) was investigated at pH 7.5 and 25 degrees C, using spectrophotometric, viscometric and molecular dynamic methods. The changes in the distance between N(epsilon2) of His(12) and N(delta1) of His(119) at the catalytic center of RNase A upon the addition of sodium sulfate, sodium hydrogen sulfate and sodium thiocyanate were evaluated by molecular dynamic methods. The compactness and expansion in terms of Stokes radius of RNase A upon the addition of sulfate ions as kosmotropic salts, and thiocyanate ion as a chaotropic salt, were estimated by viscometric measurements. Enzyme activity was measured using cytidine 2', 3'-cyclic monophosphate as a substrate. The results from the measurements of distances between N(epsilon2) of His(12) and N(delta1) of His(119) and Stokes radius suggest (i) that the presence of sulfate ions decreases the distance between the catalytic His residues and increases the globular compactness, and (ii) that there is an expansion of the enzyme surface as well as elongation of the catalytic center in the presence of thiocyanate ion. These findings are in agreement with activity measurements