Blur, eye movements and performance on a driving visual recognition slide test

Purpose Optical blur and ageing are known to affect driving performance but their effects on drivers' eye movements are poorly understood. This study examined the effects of optical blur and age on eye movement patterns and performance on the DriveSafe slide recognition test which is purported to predict fitness to drive. Methods Twenty young (27.1 ± 4.6 years) and 20 older (73.3 ± 5.7 years) visually normal drivers performed the DriveSafe under two visual conditions: best-corrected vision and with +2.00 DS blur. The DriveSafe is a Visual Recognition Slide Test that consists of brief presentations of static, real-world driving scenes containing different road users (pedestrians, bicycles and vehicles). Participants reported the types, relative positions and direction of travel of the road users in each image; the score was the number of correctly reported items (maximum score of 128). Eye movements were recorded while participants performed the DriveSafe test using a Tobii TX300 eye tracking system. Results There was a significant main effect of blur on DriveSafe scores (best-corrected: 114.9 vs blur: 93.2; p < 0.001). There was also a significant age and blur interaction on the DriveSafe scores (p < 0.001) such that the young drivers were more negatively affected by blur than the older drivers (reductions of 22% and 13% respectively; p < 0.001): with best-corrected vision, the young drivers performed better than the older drivers (DriveSafe scores: 118.4 vs 111.5; p = 0.001), while with blur, the young drivers performed worse than the older drivers (88.6 vs 95.9; p = 0.009). For the eye movement patterns, blur significantly reduced the number of fixations on road users (best-corrected: 5.1 vs blur: 4.5; p < 0.001), fixation duration on road users (2.0 s vs 1.8 s; p < 0.001) and saccade amplitudes (7.4° vs 6.7°; p < 0.001). A main effect of age on eye movements was also found where older drivers made smaller saccades than the young drivers (6.7° vs 7.4°; p < 0.001). Conclusions Blur reduced DriveSafe scores for both age groups and this effect was greater for the young drivers. The decrease in number of fixations and fixation duration on road users, as well as the reduction in saccade amplitudes under the blurred condition, highlight the difficulty experienced in performing the task in the presence of optical blur, which suggests that uncorrected refractive errors may have a detrimental impact on aspects of driving performance.

The role of tunnel junction resistances and defects on electron transport mechanism in networks of two-dimensional disordered conductors

The effect of tunnel junction resistances on the electronic property and the magneto-resistance of few-layer graphene sheet networks is investigated. By decreasing the tunnel junction resistances, transition from strong localization to weak localization occurs and magneto-resistance changes from positive to negative. It is shown that the positive magneto-resistance is due to Zeeman splitting of the electronic states at the Fermi level as it changes with the bias voltage. As the tunnel junction resistances decrease, the network resistance is well described by 2D weak localization model. Sensitivity of the magneto-resistance to the bias voltage becomes negligible and diminishes with increasing temperature. It is shown 2D weak localization effect mainly occurs inside of the few-layer graphene sheets and the minimum temperature of 5 K in our experiments is not sufficiently low to allow us to observe 2D weak localization effect of the networks as it occurs in 2D disordered metal films. Furthermore, defects inside the few-layer graphene sheets have negligible effect on the resistance of the networks which have small tunnel junction resistances between few-layer graphene sheets

Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls

Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with diseaseIRGM for Crohns disease, HLA for Crohns disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetesalthough in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases. © 2010 Macmillan Publishers Limited. All rights reserved.

Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refi nements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2∙4 billion and 1∙6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537∙6 million in 1990 to 764∙8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114∙87 per 1000 people to 110∙31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21·1% in 1990 to 31·2% in 2013. Interpretation Ageing of the world’s population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to nonfatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Cardiovascular diseases and vulnerable plaques: data, modeling, predictions and clinical applications PREFACE

Introduction Two symposia on “cardiovascular diseases and vulnerable plaques” Cardiovascular disease (CVD) is the leading cause of death worldwide. Huge effort has been made in many disciplines including medical imaging, computational modeling, bio- mechanics, bioengineering, medical devices, animal and clinical studies, population studies as well as genomic, molecular, cellular and organ-level studies seeking improved methods for early detection, diagnosis, prevention and treatment of these diseases [1-14]. However, the mechanisms governing the initiation, progression and the occurrence of final acute clinical CVD events are still poorly understood. A large number of victims of these dis- eases who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs [8,9]. Most cardiovascular diseases are associated with vulnerable plaques. A grand challenge here is to develop new imaging techniques, predictive methods and patient screening tools to identify vulnerable plaques and patients who are more vulnerable to plaque rupture and associated clinical events such as stroke and heart attack, and recommend proper treatment plans to prevent those clinical events from happening. Articles in this special issue came from two symposia held recently focusing on “Cardio-vascular Diseases and Vulnerable Plaques: Data, Modeling, Predictions and Clinical Applications.” One was held at Worcester Polytechnic Institute (WPI), Worcester, MA, USA, July 13-14, 2014, right after the 7th World Congress of Biomechanics. This symposium was endorsed by the World Council of Biomechanics, and partially supported by a grant from NIH-National Institute of Biomedical Image and Bioengineering. The other was held at Southeast University (SEU), Nanjing, China, April 18-20, 2014.

Eye movements and road hazard detection: Effects of blur and distractors

Purpose To examine the effects of optical blur, auditory distractors and age on eye movement patterns while performing a driving hazard perception test (HPT). Methods Twenty young (mean age 27.1 ± 4.6 years) and 20 older (73.3 ± 5.7 years) drivers with normal vision completed a HPT in a repeated-measures counterbalanced design while their eye movements were recorded. Testing was performed under two visual (best-corrected vision and with +2.00DS blur) and two distractor (with and without auditory distraction) conditions. Participants were required to respond to road hazards appearing in the HPT videos of real-world driving scenes and their hazard response times were recorded. Results Blur and distractors each significantly delayed hazard response time, by 0.42 and 0.76s respectively (p<0.05). A significant interaction between age and distractors indicated that older drivers were more affected by distractors than young drivers (response with distractors delayed by 0.96 and 0.60s respectively). There were no other two- or three-way interaction effect on response time. With blur, both groups fixated significantly longer on hazards before responding compared to best-corrected vision. In the presence of distractors, both groups exhibited delayed first fixation on the hazards and spent less time fixating on the hazards. There were also significant differences in eye movement characteristics between groups, where older drivers exhibited smaller saccades, delayed first fixation on hazards, and shorter fixation duration on hazards compared to the young drivers. Conclusions Collectively, the findings of delayed hazard response times and alterations in eye movement patterns with blur and distractors provide further evidence that visual impairment and distractors are independently detrimental to driving safety given that delayed hazard response times are linked to increased crash risk.

Automatic segmentation of choroidal thickness in optical coherence tomography

The assessment of choroidal thickness from optical coherence tomography (OCT) images of the human choroid is an important clinical and research task, since it provides valuable information regarding the eye’s normal anatomy and physiology, and changes associated with various eye diseases and the development of refractive error. Due to the time consuming and subjective nature of manual image analysis, there is a need for the development of reliable objective automated methods of image segmentation to derive choroidal thickness measures. However, the detection of the two boundaries which delineate the choroid is a complicated and challenging task, in particular the detection of the outer choroidal boundary, due to a number of issues including: (i) the vascular ocular tissue is non-uniform and rich in non-homogeneous features, and (ii) the boundary can have a low contrast. In this paper, an automatic segmentation technique based on graph-search theory is presented to segment the inner choroidal boundary (ICB) and the outer choroidal boundary (OCB) to obtain the choroid thickness profile from OCT images. Before the segmentation, the B-scan is pre-processed to enhance the two boundaries of interest and to minimize the artifacts produced by surrounding features. The algorithm to detect the ICB is based on a simple edge filter and a directional weighted map penalty, while the algorithm to detect the OCB is based on OCT image enhancement and a dual brightness probability gradient. The method was tested on a large data set of images from a pediatric (1083 B-scans) and an adult (90 B-scans) population, which were previously manually segmented by an experienced observer. The results demonstrate the proposed method provides robust detection of the boundaries of interest and is a useful tool to extract clinical data.

Prevalence of chronic ocular diseases in a genetic isolate : the Norfolk Island Eye Study (NIES)

Purpose: Over 40% of the permanent population of Norfolk Island possesses a unique genetic admixture dating to Pitcairn Island in the late 18 th century, with descendents having varying degrees of combined Polynesian and European ancestry. We conducted a population-based study to determine the prevalence and causes of blindness and low vision on Norfolk Island. Methods: All permanent residents of Norfolk Island aged ≥ 15 years were invited to participate. Participants completed a structured questionnaire/interview and underwent a comprehensive ophthalmic examination including slit-lamp biomicroscopy. Results: We recruited 781 people aged ≥ 15, equal to 62% of the permanent population, 44% of whom could trace their ancestry to Pitcairn Island. No one was bilaterally blind. Prevalence of unilateral blindness (visual acuity [VA] < 6/60) in those aged ≥ 40 was 1.5%. Blindness was more common in females (P=0.049) and less common in people with Pitcairn Island ancestry (P<0.001). The most common causes of unilateral blindness were age-related macular degeneration (AMD), amblyopia, and glaucoma. Five people had low vision (Best-Corrected VA < 6/18 in better eye), with 4 (80%) due to AMD. People with Pitcairn Island ancestry had a lower prevalence of AMD (P<0.001) but a similar prevalence of glaucoma to those without Pitcairn Island ancestry. Conclusions: The prevalence of blindness and visual impairment in this isolated Australian territory is low, especially amongst those with Pitcairn Island ancestry. AMD was the most common cause of unilateral blindness and low vision. The distribution of chronic ocular diseases on Norfolk Island is similar to mainland Australian estimates.

Dopamine and visually regulated eye growth in chick

Retinal image properties such as contrast and spatial frequency play important roles in the development of normal vision. For example, visual environments comprised solely of low contrast and/or low spatial frequencies induce myopia. The visual image is processed by the retina and it then locally controls eye growth. In terms of the retinal neurotransmitters that link visual stimuli to eye growth, there is strong evidence to suggest involvement of the retinal dopamine (DA) system. For example, effectively increasing retinal DA levels by using DA agonists can suppress the development of form-deprivation myopia (FDM). However, whether visual feedback controls eye growth by modulating retinal DA release, and/or some other factors, is still being elucidated. This thesis is chiefly concerned with the relationship between the dopaminergic system and retinal image properties in eye growth control. More specifically, whether the amount of retinal DA release reduces as the complexity of the image degrades was determined. For example, we investigated whether the level of retinal DA release decreased as image contrast decreased. In addition, the effects of spatial frequency, spatial energy distribution slope, and spatial phase on retinal DA release and eye growth were examined. When chicks were 8-days-old, a cone-lens imaging system was applied monocularly (+30 D, 3.3 cm cone). A short-term treatment period (6 hr) and a longer-term treatment period (4.5 days) were used. The short-term treatment tests for the acute reduction in DA release by the visual stimulus, as is seen with diffusers and lenses, whereas the 4.5 day point tests for reduction in DA release after more prolonged exposure to the visual stimulus. In the contrast study, 1.35 cyc/deg square wave grating targets of 95%, 67%, 45%, 12% or 4.2% contrast were used. Blank (0% contrast) targets were included for comparison. In the spatial frequency study, both sine and square wave grating targets with either 0.017 cyc/deg and 0.13 cyc/deg fundamental spatial frequencies and 95% contrast were used. In the spectral slope study, 30% root-mean-squared (RMS) contrast fractal noise targets with spectral fall-off of 1/f0.5, 1/f and 1/f2 were used. In the spatial alignment study, a structured Maltese cross (MX) target, a structured circular patterned (C) target and the scrambled versions of these two targets (SMX and SC) were used. Each treatment group comprised 6 chicks for ocular biometry (refraction and ocular dimension measurement) and 4 for analysis of retinal DA release. Vitreal dihydroxyphenylacetic acid (DOPAC) was analysed through ion-paired reversed phase high performance liquid chromatography with electrochemical detection (HPLC-ED), as a measure of retinal DA release. For the comparison between retinal DA release and eye growth, large reductions in retinal DA release possibly due to the decreased light level inside the cone-lens imaging system were observed across all treated eyes while only those exposed to low contrast, low spatial frequency sine wave grating, 1/f2, C and SC targets had myopic shifts in refraction. Amongst these treatment groups, no acute effect was observed and longer-term effects were only found in the low contrast and 1/f2 groups. These findings suggest that retinal DA release does not causally link visual stimuli properties to eye growth, and these target induced changes in refractive development are not dependent on the level of retinal DA release. Retinal dopaminergic cells might be affected indirectly via other retinal cells that immediately respond to changes in the image contrast of the retinal image.

Correlating eye gaze direction, depth and vehicle information on an interactive map for driver training

The over represented number of novice drivers involved in crashes is alarming. Driver training is one of the interventions aimed at mitigating the number of crashes that involve young drivers. Experienced drivers have better hazard perception ability compared to inexperienced drivers. Eye gaze patterns have been found to be an indicator of the driver's competency level. The aim of this paper is to develop an in-vehicle system which correlates information about the driver's gaze and vehicle dynamics, which is then used to assist driver trainers in assessing driving competency. This system allows visualization of the complete driving manoeuvre data on interactive maps. It uses an eye tracker and perspective projection algorithms to compute the depth of gaze and plots it on Google maps. This interactive map also features the trajectory of the vehicle and turn indicator usage. This system allows efficient and user friendly analysis of the driving task. It can be used by driver trainers and trainees to understand objectively the risks encountered during driving manoeuvres. This paper presents a prototype that plots the driver's eye gaze depth and direction on an interactive map along with the vehicle dynamics information. This prototype will be used in future to study the difference in gaze patterns in novice and experienced drivers prior to a certain manoeuvre.

When and how to treat pulmonary non-tuberculous mycobacterial diseases

Nontuberculous mycobacteria are ubiquitous environmental organisms that have been recognised as a cause of pulmonary infection for over 50 years. Traditionally patients have had underlying risk factors for development of disease; however the proportion of apparently immunocompetent patients involved appears to be rising. Not all patients culture-positive for mycobacteria will have progressive disease, making the diagnosis difficult, though criteria to aid in this process are available. The two main forms of disease are cavitary disease (usually involving the upper lobes) and fibronodular bronchiectasis (predominantly middle and lingular lobes). For patients with disease, combination antibiotic therapy for 12-24 months is generally required for successful treatment, and this may be accompanied by drug intolerances and side effects. Published success rates range from 30-82%. As the progression of disease is variable, for some patients, attention to pulmonary hygiene and underlying diseases without immediate antimycobacterial therapy may be more appropriate. Surgery can be a useful adjunct, though is associated with risks. Randomised controlled trials in well described patients would provide stronger evidence-based data to guide therapy of NTM lung diseases, and thus are much needed.