Visual Processing in Reading Disorders and Attention-Deficit/Hyperactivity Disorder and Its Contribution to Basic Reading Ability

Whether visual processing deficits are common in reading disorders (RD), and related to reading ability in general, has been debated for decades. The type of visual processing affected also is debated, although visual discrimination and short-term memory (STM) may be more commonly related to reading ability. Reading disorders are frequently comorbid with ADHD, and children with ADHD often have subclinical reading problems. Hence, children with ADHD were used as a comparison group in this study. ADHD and RD may be dissociated in terms of visual processing. Whereas RD may be associated with deficits in visual discrimination and short-term memory for order, ADHD is associated with deficits in visual-spatial processing. Thus, we hypothesized that children with RD would perform worse than controls and children with ADHD only on a measure of visual discrimination and a measure of visual STM that requires memory for order. We expected all groups would perform comparably on the measure of visual STM that does not require sequential processing. We found children with RD or ADHD were commensurate to controls on measures of visual discrimination and visual STM that do not require sequential processing. In contrast, both RD groups (RD, RD/ADHD) performed worse than controls on the measure of visual STM that requires memory for order, and children with comorbid RD/ADHD performed worse than those with ADHD. In addition, of the three visual measures, only sequential visual STM predicted reading ability. Hence, our findings suggest there is a deficit in visual sequential STM that is specific to RD and is related to basic reading ability. The source of this deficit is worthy of further research, but it may include both reduced memory for order and poorer verbal mediation

Highly Variable Taxa-specific Coral Bleaching Responses to Thermal Stresses

Complex histories of chronic and acute sea surface temperature (SST) stresses are expected to trigger taxon- and location-specific responses that will ultimately lead to novel coral communities. The 2016 El Niño-Southern Oscillation provided an opportunity to examine large- scale and recent environmental histories on emerging patterns in 226 coral communities distrib- uted across 12 countries from East Africa to Fiji. Six main coral communities were identified that largely varied across a gradient of Acropora to massive Porites dominance. Bleaching intensity was taxon-specific and was associated with complex interactions among the 20 environmental variables that we examined. Coral community structure was better aligned with the historical temperature patterns between 1985 and 2015 than the 2016 extreme temperature event. Addi- tionally, bleaching responses observed during 2016 differed from historical reports during past warm years. Consequently, coral communities present in 2016 are likely to have been reorganized by both long-term community change and acclimation mechanisms. For example, less disturbed sites with cooler baseline temperatures, higher mean historical SST background variability, and infrequent extreme warm temperature stresses were associated with Acropora-dominated communities, while more disturbed sites with lower historical SST background variability and frequent acute warm stress were dominated by stress-resistant massive Porites corals. Overall, the combination of taxon-specific responses, community-level reorganization over time, geographic variation, and multiple environmental stressors suggest complex responses and a diversity of future coral communities that can help contextualize management priorities and activities

Large Geographic Variability in the Resistance of Corals to Thermal Stress

Aim: Predictions for the future of coral reefs are largely based on thermal exposure and poorly account for potential geographic variation in biological sensitivity to ther- mal stress. Without accounting for complex sensitivity responses, simple climate ex- posure models and associated predictions may lead to poor estimates of future coral survival and lead to policies that fail to identify and implement the most appropri- ate interventions. To begin filling this gap, we evaluated a number of attributes of coral taxa and communities that are predicted to influence coral resistance to thermal stress over a large geographic range. Location: Western Indo-Pacific and Central Indo-Pacific Ocean Realms. Major taxa studied: Zooxanthellate Scleractinia – hard corals. Methods: We evaluated the geographic variability of coral resistance to thermal stress as the ratio of thermal exposure and sensitivity in 12 countries during the 2016 global-bleaching event. Thermal exposure was estimated by two metrics: (a) histori- cal excess summer heat (cumulative thermal anomaly, CTA), and (b) a multivariate index of sea-surface temperature (SST), light, and water flow (climate exposure, CE). Sensitivity was estimated for 226 sites using coordinated bleaching observations and underwater surveys of coral communities. We then evaluated coral resistance to ther- mal stress using 48 generalized linear mixed models (GLMMs) to compare the poten- tial influences of geography, historical SST variation, coral cover and coral richness. Results: Geographic faunal provinces and ecoregions were the strongest predic- tors of coral resistance to thermal stress, with sites in the Australian, Indonesian and Fiji-Caroline Islands coral provinces having higher resistance to thermal stress than Africa-India and Japan-Vietnam provinces. Ecoregions also showed strong gradients in resistance with highest resistance to thermal stress in the western Pacific and Coral Triangle and lower resistance in the surrounding ecoregions. A more detailed evaluation of Coral Triangle and non-Coral Triangle sites found higher resistance to thermal stress within the Coral Triangle, associated with c. 2.5 times more recent historical thermal anomalies and more centralized, warmer, and cool-water skew SST distributions, than in non-Coral Triangle sites. Our findings identify the importance of environmental history and geographic context in future predictions of bleaching, and identify some potential drivers of coral resistance to thermal stress. Main conclusions: Simple threshold models of heat stress and coral acclimation are commonly used to predict the future of coral reefs. Here and elsewhere we show that large-scale responses of coral communities to heat stress are geographically variable and associated with differential environmental stresses and histories

Integration of Sequence Data from a Consanguineous Family with Genetic Data from an Outbred Population Identifies PLB1 as a Candidate Rheumatoid Arthritis Risk Gene

Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R) mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009). We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2×10−6). Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry), and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT). Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted

Whole-exome sequencing and clinical interpretation of FFPE tumor samples to guide precision cancer medicine

Translating whole exome sequencing (WES) for prospective clinical use may impact the care of cancer patients; however, multiple innovations are necessary for clinical implementation. These include: (1) rapid and robust WES from formalin-fixed paraffin embedded (FFPE) tumor tissue, (2) analytical output similar to data from frozen samples, and (3) clinical interpretation of WES data for prospective use. Here, we describe a prospective clinical WES platform for archival FFPE tumor samples. The platform employs computational methods for effective clinical analysis and interpretation of WES data. When applied retrospectively to 511 exomes, the interpretative framework revealed a “long tail” of somatic alterations in clinically important genes. Prospective application of this approach identified clinically relevant alterations in 15/16 patients. In one patient, previously undetected findings guided clinical trial enrollment leading to an objective clinical response. Overall, this methodology may inform the widespread implementation of precision cancer medicine

Early Science with the Large Millimeter Telescope: Detection of Dust Emission in Multiple Images of a Normal Galaxy at z \u3e 4 Lensed by a Frontier Fields Cluster

We directly detect dust emission in an optically detected, multiply imaged galaxy lensed by the Frontier Fields cluster MACSJ0717.5+3745. We detect two images of the same galaxy at 1.1 mm with the AzTEC camera on the Large Millimeter Telescope leaving no ambiguity in the counterpart identification. This galaxy, MACS0717_Az9, is at z \u3e 4 and the strong lensing model (μ=7.5) allows us to calculate an intrinsic IR luminosity of 9.7 × 1010 Le and an obscured star formation rate of 14.6 ± 4.5 Me yr−1. The unobscured star formation rate from the UV is only 4.1 ± 0.3 Me yr−1, which means the total star formation rate (18.7 ± 4.5 Me yr−1) is dominated (75%–80%) by the obscured component. With an intrinsic stellar mass of only 6.9 × 109 Me, MACS0717_Az9 is one of only a handful of z \u3e 4 galaxies at these lower masses that is detected in dust emission. This galaxy lies close to the estimated star formation sequence at this epoch. However, it does not lie on the dust obscuration relation (IRX-β) for local starburst galaxies and is instead consistent with the Small Magellanic Cloud attenuation law. This remarkable lower mass galaxy, showing signs of both low metallicity and high dust content, may challenge our picture of dust production in the early universe

Haplotypes of DNA repair and cell cycle control genes, X-ray exposure, and risk of childhood acute lymphoblastic leukemia

[[abstract]]Background: Acute leukemias of childhood are a heterogeneous group of malignancies characterized by cytogenetic abnormalities, such as translocations and changes in ploidy. These abnormalities may be influenced by altered DNA repair and cell cycle control processes. Methods: We examined the association between childhood acute lymphoblastic leukemia (ALL) and 32 genes in DNA repair and cell cycle pathways using a haplotype-based approach, among 377 childhood ALL cases and 448 controls enrolled during 1995-2002. Results: We found that haplotypes in APEX1, BRCA2, ERCC2, and RAD51 were significantly associated with total ALL, while haplotypes in NBN and XRCC4, and CDKN2A were associated with structural and numerical change subtypes, respectively. In addition, we observed statistically significant interaction between exposure to 3 or more diagnostic X-rays and haplotypes of XRCC4 on risk of structural abnormality-positive childhood ALL. Conclusions: These results support a role of altered DNA repair and cell cycle processes in the risk of childhood ALL, and show that this genetic susceptibility can differ by cytogenetic subtype and may be modified by exposure to ionizing radiation. To our knowledge, our study is the first to broadly examine the DNA repair and cell cycle pathways using a haplotype approach in conjunction with X-ray exposures in childhood ALL risk. If confirmed, future studies are needed to identify specific functional SNPs in the regions of interest identified in this analysis

Radiology in the Era of Value-Based Healthcare: A Multi-Society Expert Statement From the ACR, CAR, ESR, IS3R, RANZCR, and RSNA

Background: The Value-Based Healthcare (VBH) concept is designed to improve individual healthcare outcomes without increasing expenditure, and is increasingly being used to determine resourcing of and reimbursement for medical services. Radiology is a major contributor to patient and societal healthcare at many levels. Despite this, some VBH models do not acknowledge radiology’s central role; this may have future negative consequences for resource allocation. Methods, findings and interpretation: This multi-society paper, representing the views of Radiology Societies in Europe, the USA, Canada, Australia, and New Zealand, describes the place of radiology in VBH models and the health-care value contributions of radiology. Potential steps to objectify and quantify the value contributed by radiology to healthcare are outlined

Integration of sequence data from a consanguineous family with genetic data from an outbred population identifies PLB1 as a candidate rheumatoid arthritis risk gene

Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R) mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009). We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2×10-6). Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry), and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT). Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted. © 2014 Plenge et al