Retinal nerve fibre layer thickness profile in normal eyes using third-generation optical coherence tomography

Aims To establish four normal retinal nerve fibre layer (RNFL) thickness radial profiles based on third-generation optical coherence tomography (OCT) and to compare them with previously reported histologic measurements.Methods A total of 20 normal eyes were studied. A circular scan was adjusted to the size of the optic disc and three scans were performed with this radius and every 200 mu m thereafter, up to a distance of 1400 mu m. Four different radial sections (superotemporal, superonasal, inferonasal, and inferotemporal) were studied to establish RNFL thickness OCT profiles. Additionally, two radial scans orientated at 45 and 1351 crossing the optic disc centre were performed in six of 20 eyes, and RNFL thickness was measured at disc margin.Results Quadrant location and distance from disc margin interaction in RNFL thickness was statistically significant (P < 0.001). the RNFL thickness decreased (P < 0.001) as the distance from the disc margin increased for all sections. the measurements automatically generated by the OCT built-in software were thinner (P < 0.001) than histologic ones close to the disc margin.Conclusions Four normal OCT RNFL profiles were established and compared with histological data obtained from the same area. RNFL measurements assessed by OCT 3 were significantly thinner close to the optic disc margin.Hosp Olhos Araraquara, Glaucoma Sect, BR-14802530 Araraquara, SP, BrazilHosp Olhos Araraquara, Retina Diagnost & Treatment Div, BR-14802530 Araraquara, SP, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilUSP, Inst Fis Sao Carlos, Sao Carlos, SP, BrazilUniv So Calif, Doheny Eye Inst, Dept Ophthalmol, Los Angeles, CA USAUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Secular evolution versus hierarchical merging: galaxy evolution along the Hubble sequence, in the field and rich environments

In the current galaxy formation scenarios, two physical phenomena are invoked to build disk galaxies: hierarchical mergers and more quiescent external gas accretion, coming from intergalactic filaments. Although both are thought to play a role, their relative importance is not known precisely. Here we consider the constraints on these scenarios brought by the observation-deduced star formation history on the one hand, and observed dynamics of galaxies on the other hand: the high frequency of bars and spirals, the high frequency of perturbations such as lopsidedness, warps, or polar rings. All these observations are not easily reproduced in simulations without important gas accretion. N-body simulations taking into account the mass exchange between stars and gas through star formation and feedback, can reproduce the data, only if galaxies double their mass in about 10 Gyr through gas accretion. Warped and polar ring systems are good tracers of this accretion, which occurs from cold gas which has not been virialised in the system's potential. The relative importance of these phenomena are compared between the field and rich clusters. The respective role of mergers and gas accretion vary considerably with environment.Comment: 18 pages, 8 figures, review paper to "Penetrating Bars through Masks of Cosmic Dust: the Hubble Tuning Fork Strikes a New Note", Pilanesberg, ed. D. Block et al., Kluwe

Usability evaluation of a clinical decision support tool for osteoporosis disease management

<p>Abstract</p> <p>Background</p> <p>Osteoporosis affects over 200 million people worldwide at a high cost to healthcare systems. Although guidelines are available, patients are not receiving appropriate diagnostic testing or treatment. Findings from a systematic review of osteoporosis interventions and a series of focus groups were used to develop a functional multifaceted tool that can support clinical decision-making in osteoporosis disease management at the point of care. The objective of our study was to assess how well the prototype met functional goals and usability needs.</p> <p>Methods</p> <p>We conducted a usability study for each component of the tool--the Best Practice Recommendation Prompt (BestPROMPT), the Risk Assessment Questionnaire (RAQ), and the Customised Osteoporosis Education (COPE) sheet--using the framework described by Kushniruk and Patel. All studies consisted of one-on-one sessions with a moderator using a standardised worksheet. Sessions were audio- and video-taped and transcribed verbatim. Data analysis consisted of a combination of qualitative and quantitative analyses.</p> <p>Results</p> <p>In study 1, physicians liked that the BestPROMPT can provide customised recommendations based on risk factors identified from the RAQ. Barriers included lack of time to use the tool, the need to alter clinic workflow to enable point-of-care use, and that the tool may disrupt the real reason for the visit. In study 2, patients completed the RAQ in a mean of 6 minutes, 35 seconds. Of the 42 critical incidents, 60% were navigational and most occurred when the first nine participants were using the stylus pen; no critical incidents were observed with the last six participants that used the touch screen. Patients thought that the RAQ questions were easy to read and understand, but they found it difficult to initiate the questionnaire. Suggestions for improvement included improving aspects of the interface and navigation. The results of study 3 showed that most patients were able to understand and describe sections of the COPE sheet, and all considered discussing the information with their physicians. Suggestions for improvement included simplifying the language and improving the layout.</p> <p>Conclusions</p> <p>Findings from the three studies informed changes to the tool and confirmed the importance of usability testing on all end users to reduce errors, and as an important step in the development process of knowledge translation interventions.</p

Statin-Associated Muscular and Renal Adverse Events: Data Mining of the Public Version of the FDA Adverse Event Reporting System

OBJECTIVE: Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and to attempt to determine the rank-order of the association. METHODS: After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. RESULTS: Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. CONCLUSIONS: Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events

Three little pieces for computer and relativity

Numerical relativity has made big strides over the last decade. A number of problems that have plagued the field for years have now been mostly solved. This progress has transformed numerical relativity into a powerful tool to explore fundamental problems in physics and astrophysics, and I present here three representative examples. These "three little pieces" reflect a personal choice and describe work that I am particularly familiar with. However, many more examples could be made.Comment: 42 pages, 11 figures. Plenary talk at "Relativity and Gravitation: 100 Years after Einstein in Prague", June 25 - 29, 2012, Prague, Czech Republic. To appear in the Proceedings (Edition Open Access). Collects results appeared in journal articles [72,73, 122-124

The Role of Histone H4 Biotinylation in the Structure of Nucleosomes

Background: Post-translational modifications of histones play important roles in regulating nucleosome structure and gene transcription. It has been shown that biotinylation of histone H4 at lysine-12 in histone H4 (K12Bio-H4) is associated with repression of a number of genes. We hypothesized that biotinylation modifies the physical structure of nucleosomes, and that biotin-induced conformational changes contribute to gene silencing associated with histone biotinylation. Methodology/Principal Findings: To test this hypothesis we used atomic force microscopy to directly analyze structures of nucleosomes formed with biotin-modified and non-modified H4. The analysis of the AFM images revealed a 13% increase in the length of DNA wrapped around the histone core in nucleosomes with biotinylated H4. This statistically significant (p,0.001) difference between native and biotinylated nucleosomes corresponds to adding approximately 20 bp to the classical 147 bp length of nucleosomal DNA. Conclusions/Significance: The increase in nucleosomal DNA length is predicted to stabilize the association of DNA with histones and therefore to prevent nucleosomes from unwrapping. This provides a mechanistic explanation for the gene silencing associated with K12Bio-H4. The proposed single-molecule AFM approach will be instrumental for studying the effects of various epigenetic modifications of nucleosomes, in addition to biotinylation

Altered maternal profiles in corticotropin-releasing factor receptor 1 deficient mice

BACKGROUND: During lactation, the CNS is less responsive to the anxiogenic neuropeptide, corticotropin-releasing factor (CRF). Further, central injections of CRF inhibit maternal aggression and some maternal behaviors, suggesting decreased CRF neurotransmission during lactation supports maternal behaviors. In this study, we examined the maternal profile of mice missing the CRF receptor 1 (CRFR1). Offspring of knockout (CRFR1-/-) mice were heterozygote to offset possible deleterious effects of low maternal glucocorticoids on pup survival and all mice contained a mixed 50:50 inbred/outbred background to improve overall maternal profiles and fecundity. RESULTS: Relative to littermate wild-type (WT) controls, CRFR1-/- mice exhibited significant deficits in total time nursing, including high arched-back, on each test day. Consistent with decreased nursing, pups of CRFR1-deficient dams weighed significantly less than WT offspring. Licking and grooming of pups was significantly higher in WT mice on postpartum Day 2 and when both test days were averaged, but not on Day 3. Time off nest was higher for CRFR1-/- mice on Day 2, but not on Day 3 or when test days were averaged. Licking and grooming of pups did not differ on Day 2 when this measure was examined as a proportion of time on nest. CRFR1-/- mice showed significantly higher nest building on Day 3 and when tests were averaged. Mean pup number was almost identical between groups and no pup mortality occurred. Maternal aggression was consistently lower in CRFR1-/- mice and in some measures these differences approached, but did not reach significance. Because of high variance, general aggression results are viewed as preliminary. In terms of sites of attacks on intruders, CRFR1-/- mice exhibited significantly fewer attacks to the belly of the intruder on Day 5 and when tests were averaged. Performance on the elevated plus maze was similar between genotypes. Egr-1 expression differences in medial preoptic nucleus and c-Fos expression differences in bed nucleus of stria terminalis between genotype suggest possible sites where loss of gene alters behavioral output. CONCLUSION: Taken together, the results suggest that the presence of an intact CRFR1 receptor supports some aspects of nurturing behavior

The Main Belt Comets and ice in the Solar System

We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies