Visual Acuity Loss and Associated Risk Factors in the Retrospective Progression of Stargardt Disease Study (ProgStar Report No. 2)

PURPOSE: To examine the association between characteristics of Stargardt disease and visual acuity (VA), to estimate the longitudinal rate of VA loss, and to identify risk factors for VA loss. DESIGN: Retrospective, multicenter cohort study. PARTICIPANTS: A total of 176 patients (332 eyes) with molecularly and clinically confirmed Stargardt disease enrolled from the United States and Europe. METHODS: Standardized data report forms were used to collect retrospective data on participants' characteristics and best-corrected or presenting VA from medical charts. Linear models with generalized estimating equations were used to estimate the cross-sectional associations, and linear mixed effects models were used to estimate the longitudinal VA loss. MAIN OUTCOME MEASURES: Yearly change in VA. RESULTS: The median duration of observation was 3.6 years. At baseline, older age of symptom onset was associated with better VA, and a longer duration of symptoms was associated with worse VA. Longitudinal analysis estimated an average of 0.3 lines loss (P 30 years showed 0.4 lines slower change of VA per year (P = 0.01) compared with patients with onset age ≤14 years. CONCLUSIONS: Given the overall slow rate of VA loss, VA is unlikely to be a sensitive outcome measure for treatment trials of Stargardt disease. However, given the faster decline in younger patients and those with no or mild visual impairment, VA may be a potential outcome measure for trials targeting such subgroups of patients. These observations will need to be assessed in a prospective study bearing in mind the inherent limitations of retrospective datasets

Comparison of Short-Wavelength Reduced-Illuminance and Conventional Autofluorescence Imaging in Stargardt Macular Dystrophy

Purpose To compare grading results between short-wavelength reduced-illuminance and conventional autofluorescence imaging in Stargardt macular dystrophy. Design Reliability study. Methods setting: Moorfields Eye Hospital, London (United Kingdom). patients: Eighteen patients (18 eyes) with Stargardt macular dystrophy. observation procedures: A series of 3 fundus autofluorescence images using 3 different acquisition parameters on a custom-patched device were obtained: (1) 25% laser power and total sensitivity 87; (2) 25% laser power and freely adjusted sensitivity; and (3) 100% laser power and freely adjusted total sensitivity (conventional). The total area of 2 hypoautofluorescent lesion types (definitely decreased autofluorescence and poorly demarcated questionably decreased autofluorescence) was measured. main outcome measures: Agreement in grading between the 3 imaging methods was assessed by kappa coefficients (κ) and intraclass correlation coefficients. Results The mean ± standard deviation area for images acquired with 25% laser power and freely adjusted total sensitivity was 2.04 ± 1.87 mm2 for definitely decreased autofluorescence (n = 15) and 1.86 ± 2.14 mm2 for poorly demarcated questionably decreased autofluorescence (n = 12). The intraclass correlation coefficient (95% confidence interval) was 0.964 (0.929, 0.999) for definitely decreased autofluorescence and 0.268 (0.000, 0.730) for poorly demarcated questionably decreased autofluorescence. Conclusions Short-wavelength reduced-illuminance and conventional fundus autofluorescence imaging showed good concordance in assessing areas of definitely decreased autofluorescence. However, there was significantly higher variability between imaging modalities for assessing areas of poorly demarcated questionably decreased autofluorescence

Neuromodulation of innate immunity by remote ischaemic conditioning in humans: Experimental cross-over study.

Experimental animal studies on the mechanisms of remote ischaemic conditioning (RIC)-induced cardioprotection against ischaemia/reperfusion injury demonstrate involvement of both neuronal and humoral pathways. Autonomic parasympathetic (vagal) pathways confer organ protection through both direct innervation and/or immunomodulation, but evidence in humans is lacking. During acute inflammation, vagal release of acetylcholine suppresses CD11b expression, a critical β2-integrin regulating neutrophil adhesion to the endothelium and transmigration to sites of injury. Here, we tested the hypothesis that RIC recruits vagal activity in humans and has an anti-inflammatory effect by reducing neutrophil CD11b expression. Participants (age:50 ​± ​19 years; 53% female) underwent ultrasound-guided injection of local anaesthetic within the brachial plexus before applying 3 ​× ​8 min cycles of brachial artery occlusion using a blood pressure cuff (RICblock). RIC was repeated 6 weeks later without brachial plexus block. Masked analysers quantified vagal activity (heart rate, heart rate variability (HRV)) before, and 10 ​min after, the last cycle of RIC. RR-interval increased after RIC (reduced heart rate) by 40 ​ms (95% confidence intervals (95%CI):13-66; n ​= ​17 subjects; P ​= ​0.003). RR-interval did not change after brachial plexus blockade (mean difference: 20 ​ms (95%CI:-11 to 50); P ​= ​0.19). The high-frequency component of HRV was reduced after RICblock, but remained unchanged after RIC (P ​< ​0.001), indicating that RIC preserved vagal activity. LPS-induced CD16+CD11b+ expression in whole blood (measured by flow cytometry) was reduced by RIC (3615 median fluorescence units (95%CI:475-6754); P = 0.026), compared with 2331 units (95%CI:-3921 to 8582); P = 0.726) after RICblock. These data suggest that in humans RIC recruits vagal cardiac and anti-inflammatory mechanisms via ischaemia/reperfusion-induced activation of sensory nerve fibres that innervate the organ undergoing RIC

High Resolution Spectroscopy of Two-Dimensional Electron Systems

Spectroscopic methods involving the sudden injection or ejection of electrons in materials are a powerful probe of electronic structure and interactions. These techniques, such as photoemission and tunneling, yield measurements of the "single particle" density of states (SPDOS) spectrum of a system. The SPDOS is proportional to the probability of successfully injecting or ejecting an electron in these experiments. It is equal to the number of electronic states in the system able to accept an injected electron as a function of its energy and is among the most fundamental and directly calculable quantities in theories of highly interacting systems. However, the two-dimensional electron system (2DES), host to remarkable correlated electron states such as the fractional quantum Hall effect, has proven difficult to probe spectroscopically. Here we present an improved version of time domain capacitance spectroscopy (TDCS) that now allows us to measure the SPDOS of a 2DES with unprecedented fidelity and resolution. Using TDCS, we perform measurements of a cold 2DES, providing the first direct measurements of the single-particle exchange-enhanced spin gap and single particle lifetimes in the quantum Hall system, as well as the first observations of exchange splitting of Landau levels not at the Fermi surface. The measurements reveal the difficult to reach and beautiful structure present in this highly correlated system far from the Fermi surface.Comment: There are formatting and minor textual differences between this version and the published version in Nature (follow the DOI link below

Progressive, Transgenerational Changes in Offspring Phenotype and Epigenotype following Nutritional Transition

Induction of altered phenotypes during development in response to environmental input involves epigenetic changes. Phenotypic traits can be passed between generations by a variety of mechanisms, including direct transmission of epigenetic states or by induction of epigenetic marks de novo in each generation. To distinguish between these possibilities we measured epigenetic marks over four generations in rats exposed to a sustained environmental challenge. Dietary energy was increased by 25% at conception in F0 female rats and maintained at this level to generation F3. F0 dams showed higher pregnancy weight gain, but lower weight gain and food intake during lactation than F1 and F2 dams. On gestational day 8, fasting plasma glucose concentration was higher and β-hydroxybutyrate lower in F0 and F1 dams than F2 dams. This was accompanied by decreased phosphoenolpyruvate carboxykinase (PEPCK) and increased PPARα and carnitine palmitoyl transferase-1 mRNA expression. PEPCK mRNA expression was inversely related to the methylation of specific CpG dinucleotides in its promoter. DNA methyltransferase (Dnmt) 3a2, but not Dnmt1 or Dnmt3b, expression increased and methylation of its promoter decreased from F1 to F3 generations. These data suggest that the regulation of energy metabolism during pregnancy and lactation within a generation is influenced by the maternal phenotype in the preceding generation and the environment during the current pregnancy. The transgenerational effects on phenotype were associated with altered DNA methylation of specific genes in a manner consistent with induction de novo of epigenetic marks in each generation

Smoking characteristics of Polish immigrants in Dublin

<p>Abstract</p> <p>Background</p> <p>This study examined two main hypotheses: a) Polish immigrants' smoking estimates are greater than their Irish counterparts (b) Polish immigrants purchasing cigarettes from Poland smoke "heavier" (≥ 20 cigarettes a day) when compared to those purchasing cigarettes from Ireland. The study also set out to identify significant predictors of 'current' smoking (some days and everyday) among the Polish immigrants.</p> <p>Methods</p> <p>Dublin residents of Polish origin (n = 1,545) completed a previously validated Polish questionnaire in response to an advertisement in a local Polish lifestyle magazine over 5 weekends (July–August, 2007). The Office of Tobacco Control telephone-based monthly survey data were analyzed for the Irish population in Dublin for the same period (n = 484).</p> <p>Results</p> <p>Age-sex adjusted smoking estimates were: 47.6% (95% Confidence Interval [CI]: 47.3%; 48.0%) among the Poles and 27.8% (95% CI: 27.2%; 28.4%) among the general Irish population (p < 0.001). Of the57% of smokers (n = 345/606) who purchased cigarettes solely from Poland and the 33% (n = 198/606) who purchased only from Ireland, 42.6% (n = 147/345) and 41.4% (n = 82/198) were "heavy" smokers, respectively (p = 0.79). Employment (Odds Ratio [OR]: 2.89; 95% CI: 1.25–6.69), lower education (OR: 3.76; 95%CI: 2.46–5.74), and a longer stay in Ireland (>24 months) were significant predictors of current smoking among the Poles. An objective validation of the self-reported smoking history of a randomly selected sub-sample immigrant group, using expired carbon monoxide (CO) measurements, showed a highly significant correlation coefficient (r = 0.64) of expired CO levels with the reported number of cigarettes consumed (p < 0.0001).</p> <p>Conclusion</p> <p>Polish immigrants' smoking estimates are higher than their Irish counterparts, and particularly if employed, with only primary-level education, and are overseas >2 years.</p

Assessing the Quality of Goal Setting in Behavioural Support for Smoking Cessation and its Association with Outcomes

BACKGROUND: Smoking cessation behavioural support can be effective but practitioners differ markedly in effectiveness, possibly due to variation in the quality of delivery of key behaviour change techniques, such as goal setting (i.e. setting a quit date). OBJECTIVES: This study aimed to (i) develop a reliable method for assessing the quality of practitioners' support in setting quit dates and (ii) assess whether quality predicts initiation of abstinence as a first step to quitting. METHODS: A scale for scoring the quality of goal setting was developed from national guidance documents and applied to 85 transcribed behavioural support sessions. Inter-rater reliability was assessed. Associations between quality scores and quit attempts were assessed. RESULTS: The 10-item scale produced had good inter-rater reliability (Kappa = 0.68). Higher quality goal setting was associated with increased self-reported quit attempts (p < .001; OR = 2.60, 95 % CI 1.54-4.40). The scale components 'set a clear quit date' (χ (2) (2, N = 85) = 22.3, p < .001) and 'within an appropriate timeframe' (χ (2) (2, N = 85) = 15.5, p < .001) were independently associated with quit attempts. CONCLUSIONS: It is possible to reliably assess the quality of goal setting in smoking cessation behavioural support. Higher quality of goal setting is associated with greater likelihood of initiating quit attempts

Draft Genome Sequence of Weissella paramesenteroides STCH-BD1, Isolated from Ensiled Sorghum bicolor

This is the final version. Available on open access from the American Society for Microbiology via the DOI in this recordData availability. The draft genome sequence of W. paramesenteroides STCH-BD1 is deposited in GenBank under the accession numbers CP065045 and CP065046. Oxford Nanopore and Illumina DNA sequence reads have been deposited in the NCBI Sequence Read Archive under accession numbers SRR13083241 and SRR13083242, respectivelyWeissella paramesenteroides has potential as an industrial biocatalyst due to its ability to produce lactic acid. A novel strain of W. paramesenteroides was isolated from ensiled sorghum. The genome was sequenced using a hybrid assembly of Oxford Nanopore and Illumina data to produce a 2-Mbp genome and 22-kbp plasmid sequence.Shell International Exploration and Production, In

Data Integration Model for Air Quality: A Hierarchical Approach to the Global Estimation of Exposures to Ambient Air Pollution

This is the author accepted manuscript. Available from arXiv via the URL in this record.Air pollution is a major risk factor for global health, with both ambient and household air pollution contributing substantial components of the overall global disease burden. One of the key drivers of adverse health effects is fine particulate matter ambient pollution (PM2:5) to which an estimated 3 million deaths can be attributed annually. The primary source of information for estimating exposures has been measurements from ground monitoring networks but, although coverage is increasing, there remain regions in which monitoring is limited. Ground monitoring data therefore needs to be supplemented with information from other sources, such as satellite retrievals of aerosol optical depth and chemical transport models. A hierarchical modelling approach for integrating data from multiple sources is proposed allowing spatially-varying relationships between ground measurements and other factors that estimate air quality. Set within a Bayesian framework, the resulting Data Integration Model for Air Quality (DIMAQ) is used to estimate exposures, together with associated measures of uncertainty, on a high resolution grid covering the entire world. Bayesian analysis on this scale can be computationally challenging and here approximate Bayesian inference is performed using Integrated Nested Laplace Approximations. Model selection and assessment is performed by cross-validation with the final model offering substantial increases in predictive accuracy, particularly in regions where there is sparse ground monitoring, when compared to previous approaches: root mean square error (RMSE) reduced from 17.1 to 10.7, and population weighted RMSE from 23.1 to 12.1 gm3. Based on summaries of the posterior distributions for each grid cell, it is estimated that 92% of the world’s population reside in areas exceeding the World Health Organization’s Air Quality Guidelines.Matthew Lloyd Thomas is supported by a scholarship from the EPSRC Centre for Doctoral Training in Statistical Applied Mathematics at Bath (SAMBa), under the project EP/L015684/1. Amelia Jobling was supported for this work by WHO contracts APW 201255146 and 201255393