A Method of Drusen Measurement Based on the Geometry of Fundus Reflectance

BACKGROUND: The hallmarks of age-related macular degeneration, the leading cause of blindness in the developed world, are the subretinal deposits known as drusen. Drusen identification and measurement play a key role in clinical studies of this disease. Current manual methods of drusen measurement are laborious and subjective. Our purpose was to expedite clinical research with an accurate, reliable digital method. METHODS: An interactive semi-automated procedure was developed to level the macular background reflectance for the purpose of morphometric analysis of drusen. 12 color fundus photographs of patients with age-related macular degeneration and drusen were analyzed. After digitizing the photographs, the underlying background pattern in the green channel was leveled by an algorithm based on the elliptically concentric geometry of the reflectance in the normal macula: the gray scale values of all structures within defined elliptical boundaries were raised sequentially until a uniform background was obtained. Segmentation of drusen and area measurements in the central and middle subfields (1000 μm and 3000 μm diameters) were performed by uniform thresholds. Two observers using this interactive semi-automated software measured each image digitally. The mean digital measurements were compared to independent stereo fundus gradings by two expert graders (stereo Grader 1 estimated the drusen percentage in each of the 24 regions as falling into one of four standard broad ranges; stereo Grader 2 estimated drusen percentages in 1% to 5% intervals). RESULTS: The mean digital area measurements had a median standard deviation of 1.9%. The mean digital area measurements agreed with stereo Grader 1 in 22/24 cases. The 95% limits of agreement between the mean digital area measurements and the more precise stereo gradings of Grader 2 were -6.4 % to +6.8 % in the central subfield and -6.0 % to +4.5 % in the middle subfield. The mean absolute differences between the digital and stereo gradings 2 were 2.8 +/- 3.4% in the central subfield and 2.2 +/- 2.7% in the middle subfield. CONCLUSIONS: Semi-automated, supervised drusen measurements may be done reproducibly and accurately with adaptations of commercial software. This technique for macular image analysis has potential for use in clinical research

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

Alternative regression models to assess increase in childhood BMI

<p>Abstract</p> <p>Background</p> <p>Body mass index (BMI) data usually have skewed distributions, for which common statistical modeling approaches such as simple linear or logistic regression have limitations.</p> <p>Methods</p> <p>Different regression approaches to predict childhood BMI by goodness-of-fit measures and means of interpretation were compared including generalized linear models (GLMs), quantile regression and Generalized Additive Models for Location, Scale and Shape (GAMLSS). We analyzed data of 4967 children participating in the school entry health examination in Bavaria, Germany, from 2001 to 2002. TV watching, meal frequency, breastfeeding, smoking in pregnancy, maternal obesity, parental social class and weight gain in the first 2 years of life were considered as risk factors for obesity.</p> <p>Results</p> <p>GAMLSS showed a much better fit regarding the estimation of risk factors effects on transformed and untransformed BMI data than common GLMs with respect to the generalized Akaike information criterion. In comparison with GAMLSS, quantile regression allowed for additional interpretation of prespecified distribution quantiles, such as quantiles referring to overweight or obesity. The variables TV watching, maternal BMI and weight gain in the first 2 years were directly, and meal frequency was inversely significantly associated with body composition in any model type examined. In contrast, smoking in pregnancy was not directly, and breastfeeding and parental social class were not inversely significantly associated with body composition in GLM models, but in GAMLSS and partly in quantile regression models. Risk factor specific BMI percentile curves could be estimated from GAMLSS and quantile regression models.</p> <p>Conclusion</p> <p>GAMLSS and quantile regression seem to be more appropriate than common GLMs for risk factor modeling of BMI data.</p

Obesity and motor skills among 4 to 6-year-old children in the united states: nationally-representative surveys

Few population-based studies have assessed relationships between body weight and motor skills in young children. Our objective was to estimate the association between obesity and motor skills at 4 years and 5-6 years of age in the United States. We used repeated cross-sectional assessments of the national sample from the Early Childhood Longitudinal Survey-Birth Cohort (ECLS-B) of preschool 4-year-old children (2005-2006; n = 5 100) and 5-6-year-old kindergarteners (2006-2007; n = 4 700). Height, weight, and fine and gross motor skills were assessed objectively via direct standardized procedures. We used categorical and continuous measures of body weight status, including obesity (Body Mass Index (BMI) ≥ 95th percentile) and BMI z-scores. Multivariate logistic and linear models estimated the association between obesity and gross and fine motor skills in very young children adjusting for individual, social, and economic characteristics and parental involvement.info:eu-repo/semantics/publishe

Induction of humoral immune response to multiple recombinant Rhipicephalus appendiculatus antigens and their effect on tick feeding success and pathogen transmission

BACKGROUND: Rhipicephalus appendiculatus is the primary vector of Theileria parva, the etiological agent of East Coast fever (ECF), a devastating disease of cattle in sub-Saharan Africa. We hypothesized that a vaccine targeting tick proteins that are involved in attachment and feeding might affect feeding success and possibly reduce tick-borne transmission of T. parva. Here we report the evaluation of a multivalent vaccine cocktail of tick antigens for their ability to reduce R. appendiculatus feeding success and possibly reduce tick-transmission of T. parva in a natural host-tick-parasite challenge model. METHODS: Cattle were inoculated with a multivalent antigen cocktail containing recombinant tick protective antigen subolesin as well as two additional R. appendiculatus saliva antigens: the cement protein TRP64, and three different histamine binding proteins. The cocktail also contained the T. parva sporozoite antigen p67C. The effect of vaccination on the feeding success of nymphal and adult R. appendiculatus ticks was evaluated together with the effect on transmission of T. parva using a tick challenge model. RESULTS: To our knowledge, this is the first evaluation of the anti-tick effects of these antigens in the natural host-tick-parasite combination. In spite of evidence of strong immune responses to all of the antigens in the cocktail, vaccination with this combination of tick and parasite antigens did not appear to effect tick feeding success or reduce transmission of T. parva. CONCLUSION: The results of this study highlight the importance of early evaluation of anti-tick vaccine candidates in biologically relevant challenge systems using the natural tick-host-parasite combination

Growth charts for children with Ellis–van Creveld syndrome

Ellis–van Creveld (EvC) syndrome is a congenital malformation syndrome with marked growth retardation. In this study, specific growth charts for EvC patients were derived to allow better follow-up of growth and earlier detection of growth patterns unusual for EvC. With the use of 235 observations of 101 EvC patients (49 males, 52 females), growth charts for males and females from 0 to 20 years of age were derived. Longitudinal and cross-sectional data were collected from an earlier review of growth data in EvC, a database of EvC patients, and from recent literature. To model the growth charts, the GAMLSS package for the R statistical program was used. Height of EvC patients was compared to healthy children using Dutch growth charts. Data are presented both on a scale for age and on a scale for the square root of age. Compared to healthy Dutch children, mean height standard deviation score values for male and female EvC patients were −3.1 and −3.0, respectively. The present growth charts should be useful in the follow-up of EvC patients. Most importantly, early detection of growth hormone deficiency, known to occur in EvC, will be facilitated

PICS-Ord: unlimited coding of ambiguous regions by pairwise identity and cost scores ordination

<p>Abstract</p> <p>Background</p> <p>We present a novel method to encode ambiguously aligned regions in fixed multiple sequence alignments by 'Pairwise Identity and Cost Scores Ordination' (PICS-Ord). The method works via ordination of sequence identity or cost scores matrices by means of Principal Coordinates Analysis (PCoA). After identification of ambiguous regions, the method computes pairwise distances as sequence identities or cost scores, ordinates the resulting distance matrix by means of PCoA, and encodes the principal coordinates as ordered integers. Three biological and 100 simulated datasets were used to assess the performance of the new method.</p> <p>Results</p> <p>Including ambiguous regions coded by means of PICS-Ord increased topological accuracy, resolution, and bootstrap support in real biological and simulated datasets compared to the alternative of excluding such regions from the analysis a priori. In terms of accuracy, PICS-Ord performs equal to or better than previously available methods of ambiguous region coding (e.g., INAASE), with the advantage of a practically unlimited alignment size and increased analytical speed and the possibility of PICS-Ord scores to be analyzed together with DNA data in a partitioned maximum likelihood model.</p> <p>Conclusions</p> <p>Advantages of PICS-Ord over step matrix-based ambiguous region coding with INAASE include a practically unlimited number of OTUs and seamless integration of PICS-Ord codes into phylogenetic datasets, as well as the increased speed of phylogenetic analysis. Contrary to word- and frequency-based methods, PICS-Ord maintains the advantage of pairwise sequence alignment to derive distances, and the method is flexible with respect to the calculation of distance scores. In addition to distance and maximum parsimony, PICS-Ord codes can be analyzed in a Bayesian or maximum likelihood framework. RAxML (version 7.2.6 or higher that was developed for this study) allows up to 32-state ordered or unordered characters. A GTR, MK, or ORDERED model can be applied to analyse the PICS-Ord codes partition, with GTR performing slightly better than MK and ORDERED.</p> <p>Availability</p> <p>An implementation of the PICS-Ord algorithm is available from <url>http://scit.us/projects/ngila/wiki/PICS-Ord</url>. It requires both the statistical software, R <url>http://www.r-project.org</url> and the alignment software Ngila <url>http://scit.us/projects/ngila</url>.</p

The publics' understanding of daily caloric recommendations and their perceptions of calorie posting in chain restaurants

<p>Abstract</p> <p>Background</p> <p>Calorie posting in chain restaurants has received increasing attention as a policy lever to reduce energy intake. Little research has assessed consumer understanding of overall daily energy requirements or perceived effectiveness of calorie posting.</p> <p>Methods</p> <p>A phone survey was conducted from May 1 through 17, 2009 with 663 randomly selected, nationally-representative adults aged 18 and older, including an oversample of Blacks and Hispanics in the United States. To examine differences in responses by race and ethnicity (White, Black, and Hispanic) and gender, we compared responses by conducting chi-squared tests for differences in proportions.</p> <p>Results</p> <p>We found that most Americans were knowledgeable about energy requirements for moderately active men (78%) and women (69%), but underestimated energy requirements for inactive adults (60%). Whites had significantly higher caloric literacy and confidence about their caloric knowledge than Blacks and Hispanics (p < 0.05). As compared to their counterparts, Blacks, Hispanics and women reported a significantly higher likelihood of eating at a chain restaurant and of selecting lower calorie foods where caloric information was posted. Most Americans favored the government requiring chain restaurants to post calorie information on menus at the point of purchase (68%). Support for government mandated calorie posting in chain restaurants was significantly higher among Blacks, Hispanics and women as compared to their counterparts. The public was divided about the mode of caloric information that would best help them make a lower calorie decision; a third favored number of calories (35%) which is the current standard mode of presenting caloric information in chain restaurants, a third favored a physical activity equivalent (26%), and a third favored percentage of total energy intake (39%).</p> <p>Conclusion</p> <p>Mandating calorie posting in chain restaurants may be a useful policy tool for promoting energy balance, particularly among Blacks, Hispanics and women who have higher obesity risk.</p

Deep diversification of an AAV capsid protein by machine learning.

Modern experimental technologies can assay large numbers of biological sequences, but engineered protein libraries rarely exceed the sequence diversity of natural protein families. Machine learning (ML) models trained directly on experimental data without biophysical modeling provide one route to accessing the full potential diversity of engineered proteins. Here we apply deep learning to design highly diverse adeno-associated virus 2 (AAV2) capsid protein variants that remain viable for packaging of a DNA payload. Focusing on a 28-amino acid segment, we generated 201,426 variants of the AAV2 wild-type (WT) sequence yielding 110,689 viable engineered capsids, 57,348 of which surpass the average diversity of natural AAV serotype sequences, with 12-29 mutations across this region. Even when trained on limited data, deep neural network models accurately predict capsid viability across diverse variants. This approach unlocks vast areas of functional but previously unreachable sequence space, with many potential applications for the generation of improved viral vectors and protein therapeutics

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table