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

Variable strength of forest stand attributes and weather conditions on the questing activity of Ixodes ricinus ticks over years in managed forests

Given the ever-increasing human impact through land use and climate change on the environment, we crucially need to achieve a better understanding of those factors that influence the questing activity of ixodid ticks, a major disease-transmitting vector in temperate forests. We investigated variation in the relative questing nymph densities of Ixodes ricinus in differently managed forest types for three years (2008–2010) in SW Germany by drag sampling. We used a hierarchical Bayesian modeling approach to examine the relative effects of habitat and weather and to consider possible nested structures of habitat and climate forces. The questing activity of nymphs was considerably larger in young forest successional stages of thicket compared with pole wood and timber stages. Questing nymph density increased markedly with milder winter temperatures. Generally, the relative strength of the various environmental forces on questing nymph density differed across years. In particular, winter temperature had a negative effect on tick activity across sites in 2008 in contrast to the overall effect of temperature across years. Our results suggest that forest management practices have important impacts on questing nymph density. Variable weather conditions, however, might override the effects of forest management practices on the fluctuations and dynamics of tick populations and activity over years, in particular, the preceding winter temperatures. Therefore, robust predictions and the detection of possible interactions and nested structures of habitat and climate forces can only be quantified through the collection of long-term data. Such data are particularly important with regard to future scenarios of forest management and climate warming

Evolutionary distances in the twilight zone -- a rational kernel approach

Phylogenetic tree reconstruction is traditionally based on multiple sequence alignments (MSAs) and heavily depends on the validity of this information bottleneck. With increasing sequence divergence, the quality of MSAs decays quickly. Alignment-free methods, on the other hand, are based on abstract string comparisons and avoid potential alignment problems. However, in general they are not biologically motivated and ignore our knowledge about the evolution of sequences. Thus, it is still a major open question how to define an evolutionary distance metric between divergent sequences that makes use of indel information and known substitution models without the need for a multiple alignment. Here we propose a new evolutionary distance metric to close this gap. It uses finite-state transducers to create a biologically motivated similarity score which models substitutions and indels, and does not depend on a multiple sequence alignment. The sequence similarity score is defined in analogy to pairwise alignments and additionally has the positive semi-definite property. We describe its derivation and show in simulation studies and real-world examples that it is more accurate in reconstructing phylogenies than competing methods. The result is a new and accurate way of determining evolutionary distances in and beyond the twilight zone of sequence alignments that is suitable for large datasets.Comment: to appear in PLoS ON

Determining Material Response for Polyvinyl Butyral (PVB) in Blast Loading Situations

Protecting structures from the effect of blast loads requires the careful design of all building components. In this context, the mechanical properties of Polyvinyl Butyral (PVB) are of interest to designers as the membrane behaviour will affect the performance of laminated glass glazing when loaded by explosion pressure waves. This polymer behaves in a complex manner and is difficult to model over the wide range of strain rates relevant to blast analysis. In this study, data from experimental tests conducted at strain rates from 0.01 s−1 to 400 s−1 were used to develop material models accounting for the rate dependency of the material. Firstly, two models were derived assuming Prony series formulations. A reduced polynomial spring and a spring derived from the model proposed by Hoo Fatt and Ouyang were used. Two fits were produced for each of these models, one for low rate cases, up to 8 s−1, and one for high rate cases, from 20 s−1. Afterwards, a single model representing all rates was produced using a finite deformation viscoelastic model. This assumed two hyperelastic springs in parallel, one of which was in series with a non-linear damper. The results were compared with the experimental results, assessing the quality of the fits in the strain range of interest for blast loading situations. This should provide designers with the information to choose between the available models depending on their design needs

SREBP-2/PNPLA8 axis improves non-alcoholic fatty liver disease through activation of autophagy

Dysregulated autophagy is associated with steatosis and non-alcoholic fatty liver disease (NAFLD), however the mechanisms connecting them remain poorly understand. Here, we show that co-administration of lovastatin and ezetimibe (L/E) significantly reverses hepatic triglyceride accumulation concomitant with an increase in SREBP-2 driven autophagy in mice fed a high-fat diet (HFD). We further show that the statin mediated increase in SREBP-2 directly activates expression of patatin-like phospholipase domain-containing enzyme 8 (PNPLA8) gene, and PNPLA8 associates with autophagosomes and is associated with a decrease in cellular triglyceride. Moreover, we show that over-expression of PNPLA8 dramatically decreases hepatic steatosis through increased autophagy in hepatocytes of HFD-fed mice. Live-cell imaging analyses also reveal that PNPLA8 dynamically interacts with LC3 and we suggest that the SREBP-2/PNPLA8 axis represents a novel regulatory mechanism for lipid homeostasis. These data provide a possible mechanism for the reported beneficial effects of statins for decreasing hepatic triglyceride levels in NAFLD patients.ope

UK adults' implicit and explicit attitudes towards obesity: a cross-sectional study.

Background: Anti-fat attitudes may lead to stigmatisation of and lowered self-esteem in obese people. Examining anti-fat attitudes is warranted given that there is an association with anti-fat behaviours. Previous studies, mainly outside the UK, have demonstrated that anti-fat attitudes are increasing over time. Methods: The study was cross-sectional with a sample of 2380 participants (74.2 % female; aged 18–65 years). In an online survey participants reported demographic characteristics and completed a range of implicit and explicit measures of obesity related attitudes. Results: Perceptions of obesity were more negative than reported in previously. Main effects indicated more negative perceptions in males, younger respondents and more frequent exercisers. Attitudes about obesity differed in relation to weight category, and in general were more positive in obese than non-obese respondents. Conclusions: This is the first study to demonstrate anti-fat attitudes across different sections of the UK population. As such, this study provides the first indication of the prevalence of anti-fat attitudes in UK adults. Interventions to modify these attitudes could target specific groups of individuals with more negative perceptions as identified here. Future work would be useful that increases understanding of both implicit and explicit attitudes towards obesity

Urinary tract infections and antibiotic use in pregnancy - qualitative analysis of online forum content

Background Antibiotics are standard treatment for asymptomatic and symptomatic urinary tract infections (UTIs) in pregnancy. Their overuse, however, can contribute to antimicrobial resistance (AMR) and expose the foetus to drugs that might affect its development. Preventative behaviours are currently the best option to reduce incidences of UTIs and to avoid the use of antibiotics in pregnancy. The aim of this study was to explore women’s experiences of UTIs in pregnancy to develop an understanding of their concerns and to optimise and encourage behaviours that facilitate appropriate use of antibiotics. Methods An online pregnancy forum in the United Kingdom (UK) was used to collect data on women’s discussions of UTIs. A total of 202 individual threads generated by 675 different usernames were selected for analysis. The data was organised using NVivo 11® software and then analysed qualitatively using inductive thematic analysis. Results Women’s perceptions of UTIs and antibiotic use in pregnancy were driven by their pre-natal attachment to the foetus. UTIs were thought to be common and high risk in pregnancy, which meant that antibiotics were viewed as essential in the presence of suspected symptoms. The dominant view about antibiotics was that their use was safe and of little concern in pregnancy. Women reported an emotional reaction to developing a UTI. They coped by seeking information about behaviour change strategies to assist with recovery and through emotional support from the online forum. Conclusions Women face dual risks when they experience UTIs; the risk from the infection and the risk from antibiotic treatment. Pre-natal attachment to the foetus is highlighted in the decision making process. The focus is on the shorter term risk from UTIs while undermining the longer term risks from antibiotic use, especially the risk of AMR. A balanced view needs to be presented, and evidence-based infection prevention strategies should be promoted, to women to ensure appropriate antibiotic use in pregnancy, to address the global challenge of AMR

Tracking of fatness during childhood, adolescence and young adulthood: a 7-year follow-up study in Madeira Island, Portugal

Aims: Investigating tracking of fatness from childhood to adolescence, early adolescence to young adulthood and late adolescence to young adulthood. Subjects and methods: Participants from the Madeira Growth Study were followed during an average period of 7.2 years. Height, body mass, skin-folds and circumferences were measured, nine health- and performance-related tests were administered and the Baecke questionnaire was used to assess physical activity. Skeletal maturity was estimated using the TW3 method. Results: The prevalence of overweight plus obesity ranged from 8.2–20.0% at baseline and from 20.4–40.0% at followup, in boys. Corresponding percentages for girls were 10.6– 12.0% and 13.2–18.0%. Inter-age correlations for fatness indicators ranged from 0.43–0.77. BMI, waist circumference and sum of skin-folds at 8, 12 and 16-years old were the main predictors of these variables at 15, 19 and 23-years old, respectively. Strength, muscular endurance and aerobic fitness were negatively related to body fatness. Physical activity and maturation were independently associated with adolescent (15 years) and young adult (19 years) fatness. Conclusions: Over 7.2 years, tracking was moderate-to-high for fatness. Variance was explained by fatness indicators and to a small extent by physical fitness, physical activity and maturation

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods

Can interventions that aim to decrease Lyme disease hazard at non-domestic sites be effective without negatively affecting ecosystem health? A systematic review protocol

Background Lyme disease (LD) is the most commonly reported, broadly distributed vector-borne disease of the northern temperate zone. It is transmitted by ticks and, if untreated, can cause skin, cardiac, nervous system and musculoskeletal disease. The distribution and incidence of LD is increasing across much of North America and Western Europe. Interventions to decrease exposure to LD hazard by encouraging behavioural change have low acceptance in high risk groups, and a safe, effective human LD vaccine is not presently available. As a result, habitat level interventions to decrease LD hazard itself (i.e. levels of infected ticks) have been proposed. However, some interventions may potentially negatively affect ecosystem health, and consequentially be neither desirable, nor politically feasible. This systematic review will catalogue interventions that aim to reduce LD hazard at non-domestic sites, and examine the evidence supporting those which are unlikely to negatively affect ecosystem health. Methods The review will be carried out in two steps. First, a screening and cataloguing stage will be conducted to identify and characterise interventions to decrease LD hazard at non-domestic sites. Secondly, the subset of interventions identified during cataloguing as unlikely to negatively affect ecosystem health will be investigated. In the screening and cataloguing step literature will be collected through database searching using pre-chosen search strings, hand-searching key journals and reviewing the websites of public health bodies. Further references will be identified by contacting stakeholders and researchers. Article screening and assessment of the likely effects of interventions on ecosystem health will be carried out independently by two reviewers. A third reviewer will be consulted if disagreements arise. The cataloguing step results will be presented in tables. Study quality will then be assessed independently by two reviewers, using adapted versions of established tools developed in healthcare research. These results will be presented in a narrative synthesis alongside tables. Though a full meta-analysis is not expected to be possible, if sub-groups of studies are sufficiently similar to compare, a partial meta-analysis will be carried out