Glaucomatous optic disc changes despite normal baseline intraocular pressure in a child

Purpose: We describe a case of normal tension glaucoma in the setting of sickle cell disease in a 9-year-old patient with a five-year follow up. Observations: A 9-year-old male patient with a history of sickle cell disease presented initially at the age of 4 years for evaluation of a brief episode of nonspecific eye pain that had spontaneously resolved prior to the clinic visit. Over the course of several years, the patient was noted to have progressive optic disc cupping bilaterally, retinal nerve fiber layer thinning bilaterally, and has developed a corresponding inferior arcuate defect on automated visual field testing in the right eye, all without elevated intraocular pressures (IOP). After neuro-ophthalmic pathologies were ruled out, the patient was diagnosed with glaucoma associated with sickle cell disease and normal baseline IOP, and brimonidine therapy was initiated. Conclusions and Importance: To our knowledge, this is the first reported case of normal-tension glaucoma in a pediatric patient. Normal-tension glaucoma may be a consideration in the evaluation of pediatric glaucoma suspects, but remains a diagnosis of exclusion

Photoproduction of J/ψJ/\psi in association with a ccˉc\bar{c} pair

Based on the color-singlet model, we investigate the photoproduction of $J/\psi$ associated with a $c \bar{c}$ pair with all subprocesses including the direct, single-resolved, and double-resolved channels. The amplitude squared of these subprocesses are obtained analytically. By choosing corresponding parameters, we give theoretical predictions for the $J/\psi$ transverse momentum distributions both at the LEPII and at the future photon colliders for these subprocesses. The numerical results show that at the LEPII these processes can not give enough contributions to account for the experimental data, and it indicates that the color-octet mechanism may still be needed. At the photon collider with the laser back scattering photons, the resolved photon channe will dominate over the direct one in small and moderate $p_t$ regions with large $\sqrt{s}$. By measuring the $J/\psi$ production associated with a $c\bar{c}$ pair, this process can be separated from the inclusive $J/\psi$ production and may provide a new chance to test the color-singlet contributions.Comment: 16 pages, 7 figure

Top Quark Decays into Heavy Quark Mesons

For top quark decays into heavy quark mesons $\Upsilon$ and $\bar{B}_c^*$ , a complete calculation to the leading order both in QCD coupling constant $\alpha_s$ and in $v$, the typical velocity of the heavy quarks inside the mesons, is performed. Relatons between the top quark mass and the decay branching ratios are studied. Comparion with the results which are obtained by using the quark frangmentation functions is also discussed. The branching ratios are consistent (within a factor of $2\sim 3$) with that obtained using fragmentation functions at $m_t\sim 150$ GeV.Comment: 15 pages in LaTex form, 4 figures include

Computer-aided diagnosis for (123I)FP-CIT imaging: impact on clinical reporting

BACKGROUND: For (123I)FP-CIT imaging, a number of algorithms have shown high performance in distinguishing normal patient images from those with disease, but none have yet been tested as part of reporting workflows. This study aims to evaluate the impact on reporters' performance of a computer-aided diagnosis (CADx) tool developed from established machine learning technology. Three experienced (123I)FP-CIT reporters (two radiologists and one clinical scientist) were asked to visually score 155 reconstructed clinical and research images on a 5-point diagnostic confidence scale (read 1). Once completed, the process was then repeated (read 2). Immediately after submitting each image score for a second time, the CADx system output was displayed to reporters alongside the image data. With this information available, the reporters submitted a score for the third time (read 3). Comparisons between reads 1 and 2 provided evidence of intra-operator reliability, and differences between reads 2 and 3 showed the impact of the CADx. RESULTS: The performance of all reporters demonstrated a degree of variability when analysing images through visual analysis alone. However, inclusion of CADx improved consistency between reporters, for both clinical and research data. The introduction of CADx increased the accuracy of the radiologists when reporting (unfamiliar) research images but had less impact on the clinical scientist and caused no significant change in accuracy for the clinical data. CONCLUSIONS: The outcomes for this study indicate the value of CADx as a diagnostic aid in the clinic and encourage future development for more refined incorporation into clinical practice

Acute ACAT1/SOAT1 Blockade Increases MAM Cholesterol and Strengthens ER-Mitochondria Connectivity.

Cholesterol is a key component of all mammalian cell membranes. Disruptions in cholesterol metabolism have been observed in the context of various diseases, including neurodegenerative disorders such as Alzheimer\u27s disease (AD). The genetic and pharmacological blockade of acyl-CoA:cholesterol acyltransferase 1/sterol O-acyltransferase 1 (ACAT1/SOAT1), a cholesterol storage enzyme found on the endoplasmic reticulum (ER) and enriched at the mitochondria-associated ER membrane (MAM), has been shown to reduce amyloid pathology and rescue cognitive deficits in mouse models of AD. Additionally, blocking ACAT1/SOAT1 activity stimulates autophagy and lysosomal biogenesis; however, the exact molecular connection between the ACAT1/SOAT1 blockade and these observed benefits remain unknown. Here, using biochemical fractionation techniques, we observe cholesterol accumulation at the MAM which leads to ACAT1/SOAT1 enrichment in this domain. MAM proteomics data suggests that ACAT1/SOAT1 inhibition strengthens the ER-mitochondria connection. Confocal and electron microscopy confirms that ACAT1/SOAT1 inhibition increases the number of ER-mitochondria contact sites and strengthens this connection by shortening the distance between these two organelles. This work demonstrates how directly manipulating local cholesterol levels at the MAM can alter inter-organellar contact sites and suggests that cholesterol buildup at the MAM is the impetus behind the therapeutic benefits of ACAT1/SOAT1 inhibition

A single sub-km Kuiper Belt object from a stellar Occultation in archival data

The Kuiper belt is a remnant of the primordial Solar System. Measurements of its size distribution constrain its accretion and collisional history, and the importance of material strength of Kuiper belt objects (KBOs). Small, sub-km sized, KBOs elude direct detection, but the signature of their occultations of background stars should be detectable. Observations at both optical and X-ray wavelengths claim to have detected such occultations, but their implied KBO abundances are inconsistent with each other and far exceed theoretical expectations. Here, we report an analysis of archival data that reveals an occultation by a body with a 500 m radius at a distance of 45 AU. The probability of this event to occur due to random statistical fluctuations within our data set is about 2%. Our survey yields a surface density of KBOs with radii larger than 250 m of 2.1^{+4.8}_{-1.7} x 10^7 deg^{-2}, ruling out inferred surface densities from previous claimed detections by more than 5 sigma. The fact that we detected only one event, firmly shows a deficit of sub-km sized KBOs compared to a population extrapolated from objects with r>50 km. This implies that sub-km sized KBOs are undergoing collisional erosion, just like debris disks observed around other stars.Comment: To appear in Nature on December 17, 2009. Under press embargo until 1800 hours London time on 16 December. 19 pages; 7 figure

Safety assurance of a high voltage controller for an industrial robotic system

Due to the risk of discharge sparks and ignition, there are strict rules concerning the safety of high voltage electrostatic systems used in industrial painting robots. In order to assure that the system fulfils its safety requirements, formal verification is an important tool to supplement traditional testing and quality assurance procedures. The work in this paper presents formal verification of the most important safety functions of a high voltage controller. The controller has been modelled as a finite state machine, which was formally verified using two different model checking software tools; Simulink Design Verifier and RoboTool. Five safety critical properties were specified and formally verified using the two tools. Simulink was chosen as a low-threshold entry point since MathWorks products are well known to most practitioners. RoboTool serves as a software tool targeted towards model checking, thus providing more advanced options for the more experienced user. The comparative study and results show that all properties were successfully verified. The verification times in both tools were in the order of a few minutes, which was within the acceptable time limit for this particular application

The promise of microarrays in the management and treatment of breast cancer

Breast cancer is the most common malignancy afflicting women from Western cultures. Developments in breast cancer molecular and cellular biology research have brought us closer to understanding the genetic basis of this disease. Recent advances in microarray technology hold the promise of further increasing our understanding of the complexity and heterogeneity of this disease, and providing new avenues for the prognostication and prediction of breast cancer outcomes. These new technologies have some limitations and have yet to be incorporated into clinical use, for both the diagnosis and treatment of women with breast cancer. The most recent application of microarray genomic technologies to studying breast cancer is the focus of this review

Using the posterior distribution of deviance to measure evidence of association for rare susceptibility variants

Aitkin recently proposed an integrated Bayesian/likelihood approach that he claims is general and simple. We have applied this method, which does not rely on informative prior probabilities or large-sample results, to investigate the evidence of association between disease and the 16 variants in the KDR gene provided by Genetic Analysis Workshop 17. Based on the likelihood of logistic regression models and considering noninformative uniform prior probabilities on the coefficients of the explanatory variables, we used a random walk Metropolis algorithm to simulate the distributions of deviance and deviance difference. The distribution of probability values and the distribution of the proportions of positive deviance differences showed different locations, but the direction of the shift depended on the genetic factor. For the variant with the highest minor allele frequency and for any rare variant, standard logistic regression showed a higher power than the novel approach. For the two variants with the strongest effects on Q1 under a type I error rate of 1%, the integrated approach showed a higher power than standard logistic regression. The advantages and limitations of the integrated Bayesian/likelihood approach should be investigated using additional regions and considering alternative regression models and collapsing methods