Usability Testing of Two Ambulatory EHR Navigators

Despite widespread electronic health record (EHR) adoption, poor EHR system usability continues to be a significant barrier to effective system use for end users. One key to addressing usability problems is to employ user testing and user-centered design

Visual Prognosis after Explantation of Small-Aperture Corneal Inlays in Presbyopic Eyes: A Case Series

The purpose of this study was to report visual prognosis after explantation of a small-aperture corneal inlay used for the treatment of presbyopia. This is a retrospective case series conducted at a single site in Draper, Utah, USA (Hoopes Vision). Medical records of 176 patients who had received a small-aperture corneal inlay (KAMRA™, AcuFocus Inc., Irvine, CA, USA) were reviewed. Patients who had undergone explantation of the device were identified. Uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), corrected distance visual acuity (CDVA), and manifest refraction spherical equivalent (MRSE) were measured pre-implantation, post-implantation, pre-explantation, and post-explantation of the inlay. Ten eyes from ten patients were included in this study. The explantation rate was 5.7% over 31 months, with blurry vision as the most common complaint. After explantation, six patients achieved pre-implantation UDVA, and six achieved pre-implantation UNVA. Eight of nine patients who underwent final manifest refraction achieved pre-operative CDVA. All patients had residual donut-shaped corneal haze in the stroma at the previous position of the inlay. All patients experienced improvement in haze with 20% experiencing complete resolution. The degree of stromal haze was not related to the duration of implantation. Of the subset of patients who underwent explantation of their small-aperture corneal inlay, there was persistent loss of CDVA in 10%. The majority of patients experienced some level of residual stromal haze, which may contribute to deficits in UNVA and CDVA in few patients. A hyperopic shift induced by the corneal inlay may contribute to the blurry vision these patients experienced; there was a reduction of this shift post-explantation. While this device is removable, patients should expect some post-explantation changes such as residual haze with a small subset experiencing persistent deficits in CDVA

Analysis of Two New Arabinosyltransferases Belonging to the Carbohydrate-Active Enzyme (CAZY) Glycosyl Transferase Family1 Provides Insights into Disease Resistance and Sugar Donor Specificity

Glycosylation of small molecules is critical for numerous biological processes in plants, including hormone homeostasis, neutralization of xenobiotics, and synthesis and storage of specialized metabolites. Glycosylation of plant natural products is usually carried out by uridine diphosphate-dependent glycosyltransferases (UGTs). Triterpene glycosides (saponins) are a large family of plant natural products that determine important agronomic traits such as disease resistance and flavor and have numerous pharmaceutical applications. Most characterised plant natural product UGTs are glucosyltransferases, and little is known about enzymes that add other sugars. Here we report the discovery and characterization of AsAAT1 (UGT99D1), which is required for biosynthesis of the antifungal saponin avenacin A-1 in oat. This enzyme adds L-arabinose to the triterpene scaffold at the C-3 position, a modification critical for disease resistance. The only previously reported plant natural product arabinosyltransferase is a flavonoid arabinosyltransferase from Arabidopsis. We show that AsAAT1 has high specificity for UDP-β-L-arabinopyranose, identify two amino acids required for sugar donor specificity, and through targeted mutagenesis convert AsAAT1 into a glucosyltransferase. We further identify a second arabinosyltransferase potentially implicated in the biosynthesis of saponins that determine bitterness in soybean. Our investigations suggest independent evolution of UDP-arabinose sugar donor specificity in arabinosyltransferases in monocots and eudicots

Gristhorpe Man: an Early Bronze Age log-coffin burial scientifically defined

© 2010 Antiquity PublicationsA log-coffin excavated in the early nineteenth century proved to be well enough preserved in the early twenty-first century for the fill armoury of modern scientific investigation to give its occupants and contents new identity, new origins and a new date. In many ways the interpretation is much the same as before: a local big man buried looking out to sea. Modern analytical techniques can create a person more real, more human and more securely anchored in history. This research team shows how.The project has been funded by grants from the British Academy, British Association for the Advancement of Science, Natural Environment Research Council, Royal Archaeological Institute and Scarborough Museums Trust. CJK’s participation in this project was funded by a Leverhulme Research Fellowship (RF/6/RFG/2008/0253)

Effects of a changing environment on the aboveground and belowground systems of yellow birch (Betula alleghaniensis Britton) and sugar maple (Acer saccharum Marsh)

The environment is constantly changing. A change in one environmental factor will cause changes in many other environmental factors either simultaneously or sequentially. For example, an increase in available light, due to canopy opening by natural disturbances, may increase soil temperature and moisture on the forest floor. Therefore, a changing environment has interactive effects on the trees. In forest ecological studies, the effects of some single environmental factors on tree growth are known, but there is a lack of knowledge of the interactions between multiple factors. An understanding of the interactive effects of abiotic and biotic factors on trees is critical for an understanding of the growth and survival of understory saplings in a complex changing environment. The aboveground and belowground systems of a tree respond differently to the same abiotic factors, such as light, since these systems grow in differing environments. This thesis will focus on the interactive effects among available light (including canopy gap size), tree size, artificial shading, liming and plant competition on the aboveground and belowground systems of yellow birch and sugar maple growing in the understory in two field experiments and the interactive effects of light, elevated CO 2 and mycorrhizae on seedlings of both species in a phytotron experiment. The three investigations will address several key questions concerning the growth of these two species and the development of their mycorrhizae in a complex changing environment in the present and future

A noncanonical vacuolar sugar transferase required for biosynthesis of antimicrobial defense compounds in oat

Plants produce an array of natural products with important ecological functions. These compounds are often decorated with oligosaccharide groups that influence bioactivity, but the biosynthesis of such sugar chains is not well understood. Triterpene glycosides (saponins) are a large family of plant natural products that determine important agronomic traits, as exemplified by avenacins, antimicrobial defense compounds produced by oats. Avenacins have a branched trisaccharide moiety consisting of L-arabinose linked to 2 D-glucose molecules that is critical for antifungal activity. Plant natural product glycosylation is usually performed by uridine diphosphate-dependent glycosyltransferases (UGTs). We previously characterized the arabinosyltransferase that initiates the avenacin sugar chain; however, the enzymes that add the 2 remaining D-glucose molecules have remained elusive. Here we characterize the enzymes that catalyze these last 2 glucosylation steps. AsUGT91G16 is a classical cytosolic UGT that adds a 1,2-linked D-glucose molecule to L-arabinose. Unexpectedly, the enzyme that adds the final 1,4-linked D-glucose (AsTG1) is not a UGT, but rather a sugar transferase belonging to Glycosyl Hydrolase family 1 (GH1). Unlike classical UGTs, AsTG1 is vacuolar. Analysis of oat mutants reveals that AsTG1 corresponds to Sad3, a previously uncharacterized locus shown by mutation to be required for avenacin biosynthesis. AsTG1 and AsUGT91G16 form part of the avenacin biosynthetic gene cluster. Our demonstration that a vacuolar transglucosidase family member plays a critical role in triterpene biosynthesis highlights the importance of considering other classes of carbohydrate-active enzymes in addition to UGTs as candidates when elucidating pathways for the biosynthesis of glycosylated natural products in plants

Subtelomeric assembly of a multi-gene pathway for antimicrobial defense compounds in cereals

Non-random gene organization in eukaryotes plays a significant role in genome evolution. Here, we investigate the origin of a biosynthetic gene cluster for production of defence compounds in oat—the avenacin cluster. We elucidate the structure and organisation of this 12-gene cluster, characterise the last two missing pathway steps, and reconstitute the entire pathway in tobacco by transient expression. We show that the cluster has formed de novo since the divergence of oats in a subtelomeric region of the genome that lacks homology with other grasses, and that gene order is approximately colinear with the biosynthetic pathway. We speculate that the positioning of the late pathway genes furthest away from the telomere may mitigate against a ‘self-poisoning’ scenario in which toxic intermediates accumulate as a result of telomeric gene deletions. Our investigations reveal a striking example of adaptive evolution underpinned by remarkable genome plasticity

Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P <1.06 x 10(- 7), of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.Peer reviewe

Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (P-Bonferroni <1.06 x 10(-7)). In additional analyses in 7,278 participants,Peer reviewe

The LifeCycle Project-EU Child Cohort Network : a federated analysis infrastructure and harmonized data of more than 250,000 children and parents

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.Peer reviewe