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Retinoblastoma is the most common primary intraocular tumor of childhood with >95% survival rates in the US. Traditional therapy for retinoblastoma often included enucleation (removal of the eye). While much is known about the visual, physical, and cognitive ramifications of enucleation, data are lacking about survivors' perception of how this treatment impacts overall quality of life.
Qualitative analysis of an open-ended response describing how much the removal of an eye had affected retinoblastoma survivors' lives and in what ways in free text, narrative form.
Four hundred and four retinoblastoma survivors who had undergone enucleation (bilateral disease = 214; 52% female; mean age = 44, SD = 11) completed the survey. Survivors reported physical problems (n = 205, 50.7%), intrapersonal problems (n = 77, 19.1%), social and relational problems (n = 98, 24.3%), and affective problems (n = 34, 8.4%) at a mean of 42 years after diagnosis. Three key themes emerged from survivors' responses; specifically, they (1) continue to report physical and intrapersonal struggles with appearance and related self-consciousness due to appearance; (2) have multiple social and relational problems, with teasing and bullying being prominent problems; and (3) reported utilization of active coping strategies, including developing more acceptance and learning compensatory skills around activities of daily living.
Significance of results
This study suggests that adult retinoblastoma survivors treated with enucleation continue to struggle with a unique set of psychosocial problems. Future interventions can be designed to teach survivors more active coping skills (e.g., for appearance-related issues, vision-related issues, and teasing/bullying) to optimize survivors' long-term quality of life.
We propose the concept of the “Fish Revolution” to demarcate the dramatic increase in North Atlantic fisheries after AD 1500, which led to a 15-fold increase of cod (Gadus morhua) catch volumes and likely a tripling of fish protein to the European market. We consider three key questions: (1) What were the environmental parameters of the Fish Revolution? (2) What were the globalising effects of the Fish Revolution? (3) What were the consequences of the Fish Revolution for fishing communities? While these questions would have been considered unknowable a decade or two ago, methodological developments in marine environmental history and historical ecology have moved information about both supply and demand into the realm of the discernible. Although much research remains to be done, we conclude that this was a major event in the history of resource extraction from the sea, mediated by forces of climate change and globalisation, and is likely to provide a fruitful agenda for future multidisciplinary research.
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
This article proposes the audio reality effect as a meaningful translation of Roland Barthes’s literary reality effect to the sonic realm. This refinement of transcontextuality and source recognition is applied to electroacoustic music and soundscape composition using the works and writings of Emmerson, Truax, Wishart, Smalley, Fischman, Young, Norman and Field. Lastly, this study mimetically analyses 2 seconds / b minor / wave by Michael Pisaro and Taku Sugimoto in order to demonstrate the relevance of mimesis and the audio reality effect for understanding current musical practice.
The aim of this paper is to evaluate the compatibility between the Holocene relative sea-level (RSL) curves proposed for the Brazilian littoral and mangrove dynamics along a fluvial valley in the state of southern Bahia. This was done integrating geomorphological, sedimentological, palynological, and stable isotopic data from two cores collected at the mouth of the Jucuruçu River and at a site 23 km inland, near the city of Prado, northeastern Brazil. Core PR07, sampled from a fluvial plain at about 4.5±1 m above the RSL, reveals mangrove pollen (5–20%) and estuarine/terrestrial organic matter (δ13C=~–25‰, C/N=7.3–67) between 4.5 m (~7400 cal yr BP) and 1.75 m depth (~5350 cal yr BP). Core PR11, sampled from a mangrove tidal flat, also revealed mangrove pollen taxa (5-28%) since 660 cal yr BP. Core PR07 indicated absence of mangrove pollen and increase of sedimentary organic matter sourced from terrestrial C3 plants (δ13C=~–27‰, C/N=22–159) during the last 5350 cal yr BP. Probably, the changes in vegetation and sedimentary organic matter identified in core PR07 were caused by the combined effects of the RSL fluctuations, with a highstand at about 5350 cal yr BP of 2.7±1.35 m, and changes in fluvial discharge.
In the frame of the COST ACTION ‘EMBOS’ (Development and implementation of a pan-European Marine Biodiversity Observatory System), coverage of intertidal macroalgae was estimated at a range of marine stations along the European coastline (Subarctic, Baltic, Atlantic, Mediterranean). Based on these data, we tested whether patterns in macroalgal diversity and distribution along European intertidal rocky shores could be explained by a set of meteo-oceanographic variables. The variables considered were salinity, sea surface temperature, photosynthetically active radiation, significant wave height and tidal range and were compiled from three different sources: remote sensing, reanalysis technique and in situ measurement. These variables were parameterized to represent average conditions (mean values), variability (standard deviation) and extreme events (minimum and maximum values). The results obtained in this study contribute to reinforce the EMBOS network approach and highlight the necessity of considering meteo-oceanographic variables in long-term assessments. The broad spatial distribution of pilot sites has allowed identification of latitudinal and longitudinal gradients manifested through species composition, diversity and dominance structure of intertidal macroalgae. These patterns follow a latitudinal gradient mainly explained by sea surface temperature, but also by photosynthetically active radiation, salinity and tidal range. Additionally, a longitudinal gradient was also detected and could be linked to wave height.
Green manure crops must produce high biomass to supply biological N, increase organic matter and control weeds. The objectives of our study were to assess above-ground biomass productivity and weed suppression of clover (Trifolium spp.) green manures in an organic soybean [Glycine max (L.) Merr.]-winter wheat (Triticum aestivum L.)-corn (Zea mays L.) rotation in eastern Nebraska in three cycles (2011–12, 2012–13, 2013–14). Treatments were green manure species [red clover (T. pratense L.) and white clover (T. repens L.)] undersown into winter wheat in March and green manure mowing regime (one late summer mowing or no mowing). We measured wheat productivity and grain protein at wheat harvest, and clover and weed above-ground biomass as dry matter (DM) at wheat harvest, 35 days after wheat harvest, in October and in April before clover termination. Winter wheat grain yields and grain protein were not affected by undersown clovers. DM was higher for red than for white clover at most sampling times. Red clover produced between 0.4 and 5.5 Mg ha−1 in the fall and 0.4–5.2 Mg ha−1 in the spring. White clover produced between 0.1 and 2.5 Mg ha−1 in the fall and 0.2–3.1 Mg ha−1 in the spring. Weed DM was lower under red clover than under white clover at most sampling times. In the spring, weed DM ranged from 0.0 to 0.6 Mg ha−1 under red clover and from 0.0 to 3.1 Mg ha−1 under white clover. Mowing did not consistently affect clover or weed DM. For organic growers in eastern Nebraska, red clover undersown into winter wheat can be a productive green manure with good weed suppression potential.
Examining how variability in population abundance and distribution is allotted among different spatial scales can inform of processes that are likely to generate that variability. Results of studies dealing with scale issues in marine benthic communities suggest that variability is concentrated at small spatial scales (from tens of centimetres to few metres) and that spatial patterns of variation are consistent across ecosystems characterized by contrasting physical and biotic conditions, but this has not been formally tested. Here we quantified the variability in the distribution of intertidal rocky shore communities at a range of spatial scales, from tens of centimetres to thousands of kilometres, both in the NE Atlantic and the Mediterranean, and tested whether the observed patterns differed between the two basins. We focused on canopy-forming macroalgae and associated understorey assemblages in the low intertidal, and on the distribution of Patella limpets at mid intertidal levels. Our results highlight that patterns of spatial variation, at each scale investigated, were consistent between the Atlantic and the Mediterranean, suggesting that similar ecological processes operate in these regions. In contrast with former studies, variability in canopy cover, species richness and limpet abundance was equally distributed among spatial scales, possibly reflecting the fingerprint of multiple processes. Variability in community structure of low intertidal assemblages, instead, peaked at the largest scale, suggesting that oceanographic processes and climatic gradients may be important. We conclude that formal comparisons of variability across scales nested in contrasting systems are needed, before any generalization on patterns and processes can be made.
Coastal ecosystems are highly complex and driven by multiple environmental factors. To date we lack scientific evidence for the relative contribution of natural and anthropogenic drivers for the majority of marine habitats in order to adequately assess the role of different stressors across the European seas. Such relationship can be investigated by analysing the correlation between environmental variables and biotic patterns in multivariate space and taking into account non-linearities. Within the framework of the EMBOS (European Marine Biodiversity Observatory System) programme, hard bottom intertidal communities were sampled in a standardized way across European seas. Links between key natural and anthropogenic drivers and hard bottom communities were analysed using Boosted Regression Trees modelling. The study identified strong interregional variability and showed that patterns of hard bottom macroalgal and invertebrate communities were primarily a function of tidal regime, nutrient loading and water temperature (anomalies). The strength and shape of functional form relationships varied widely however among types of organisms (understorey algae composing mostly filamentous species, canopy-forming algae or sessile invertebrates) and aggregated community variables (cover or richness). Tidal regime significantly modulated the effect of nutrient load on the cover and richness of understorey algae and sessile invertebrates. In contrast, hydroclimate was more important for canopy algae and temperature anomalies and hydroclimate separately or interactively contributed to the observed patterns. The analyses also suggested that climate-induced shifts in weather patterns may result in the loss of algal richness and thereby in the loss of functional diversity in European hard bottom intertidal areas.
Within the COST action EMBOS (European Marine Biodiversity Observatory System) the degree and variation of the diversity and densities of soft-bottom communities from the lower intertidal or the shallow subtidal was measured at 28 marine sites along the European coastline (Baltic, Atlantic, Mediterranean) using jointly agreed and harmonized protocols, tools and indicators. The hypothesis tested was that the diversity for all taxonomic groups would decrease with increasing latitude. The EMBOS system delivered accurate and comparable data on the diversity and densities of the soft sediment macrozoobenthic community over a large-scale gradient along the European coastline. In contrast to general biogeographic theory, species diversity showed no linear relationship with latitude, yet a bell-shaped relation was found. The diversity and densities of benthos were mostly positively correlated with environmental factors such as temperature, salinity, mud and organic matter content in sediment, or wave height, and related with location characteristics such as system type (lagoons, estuaries, open coast) or stratum (intertidal, subtidal). For some relationships, a maximum (e.g. temperature from 15–20°C; mud content of sediment around 40%) or bimodal curve (e.g. salinity) was found. In lagoons the densities were twice higher than in other locations, and at open coasts the diversity was much lower than in other locations. We conclude that latitudinal trends and regional differences in diversity and densities are strongly influenced by, i.e. merely the result of, particular sets and ranges of environmental factors and location characteristics specific to certain areas, such as the Baltic, with typical salinity clines (favouring insects) and the Mediterranean, with higher temperatures (favouring crustaceans). Therefore, eventual trends with latitude are primarily indirect and so can be overcome by local variation of environmental factors.
Methylation of the fragile X mental retardation 1 (FMR1) exon 1/intron 1 boundary positioned fragile X related epigenetic element 2 (FREE2), reveals skewed X-chromosome inactivation (XCI) in fragile X syndrome full mutation (FM: CGG > 200) females. XCI skewing has been also linked to abnormal X-linked gene expression with the broader clinical impact for sex chromosome aneuploidies (SCAs). In this study, 10 FREE2 CpG sites were targeted using methylation specific quantitative melt analysis (MS-QMA), including 3 sites that could not be analysed with previously used EpiTYPER system. The method was applied for detection of skewed XCI in FM females and in different types of SCA. We tested venous blood and saliva DNA collected from 107 controls (CGG < 40), and 148 FM and 90 SCA individuals. MS-QMA identified: (i) most SCAs if combined with a Y chromosome test; (ii) locus-specific XCI skewing towards the hypomethylated state in FM females; and (iii) skewed XCI towards the hypermethylated state in SCA with 3 or more X chromosomes, and in 5% of the 47,XXY individuals. MS-QMA output also showed significant correlation with the EpiTYPER reference method in FM males and females (P < 0.0001) and SCAs (P < 0.05). In conclusion, we demonstrate use of MS-QMA to quantify skewed XCI in two applications with diagnostic utility.
It is unclear if children of different weight status differ in their nutritional habits while watching television. The objective of the present paper was to determine if children who are overweight or obese differ in their frequency of consumption of six food items while watching television compared with their normal-weight counterparts. A cross-sectional study of 550 children (57·1 % female; mean age = 10 years) from Ottawa, Canada was conducted. Children's weight status was categorised using the Centers for Disease Control and Prevention cut-points. Questionnaires were used to determine the number of hours of television watching per day and the frequency of consumption of six types of foods while watching television. Overweight/obese children watched more television per day than normal-weight children (3·3 v. 2·7 h, respectively; P = 0·001). Obese children consumed fast food and fruits/vegetables more frequently while watching television than normal-weight or overweight children (P < 0·05). Children who watched more than 4 h of television per d had higher odds (OR 3·21; 95% CI 1·14, 9·03; P = 0·03) of being obese, independent of several covariates, but not independent of moderate-to-vigorous physical activity. The finding that both television watching and the frequency of consumption of some food items during television watching are higher in children who are obese is concerning. While the nature of the present study does not allow for the determination of causal pathways, future research should investigate these weight-status differences to identify potential areas of intervention.
The mean air temperature of the Icelandic interior is below 10 °C. However, we have previously observed 16S rDNA sequences associated with thermophilic lineages in Icelandic basalts. Measurements of the temperatures of igneous rocks in Iceland showed that solar insolation of these low albedo substrates achieved a peak surface temperature of 44.5 °C. We isolated seven thermophilic Geobacillus species from basalt with optimal growth temperatures of ~65 °C. The minimum growth temperature of these organisms was ~36 °C, suggesting that they could be active in the rock environment. Basalt dissolution rates at 40 °C were increased in the presence of one of the isolates compared to abiotic controls, showing its potential to be involved in active biogeochemistry at environmental temperatures. These data raise the possibility of transient active thermophilic growth in macroclimatically cold rocky environments, implying that the biogeographical distribution of active thermophiles might be greater than previously understood. These data show that temperatures measured or predicted over large scales on a planet are not in themselves adequate to assess niches available to extremophiles at micron scales.