Remote severity assessment in atopic dermatitis:Validity and reliability of the remote Eczema Area and Severity Index and Self-Administered Eczema Area and Severity Index

Background: Reliable assessment of atopic dermatitis (AD) severity is necessary for clinical practice and research. Valid and reliable remote assessment is essential to facilitate remote care and research. Objectives: Assess the validity and reliability of the Eczema Area and Severity Index (EASI) based on images and patient-assessed severity based on the Self-Administered EASI (SA-EASI). Methods: Whole-body clinical images were taken during consultation from children with AD. After consultations, caregivers completed the SA-EASI and provided images from home. Four raters assessed all images twice using EASI. Results: A total of 1534 clinical images and 425 patient-provided images were collected from 87 and 32 children. Excellent (0.90) validity, good inter (0.77) and intrarater reliability (0.91), and standard error of measurement (4.31) was found for the EASI based on clinical images. Feasibility of patient-provided images showed limitations with missing images (43.8%) and quality issues (23.1%). However, good validity (0.86), inter (0.74) and intrarater reliability (0.94) were found when assessment was possible. Moderate correlation (0.60) between SA-EASI and EASI was found. Limitations: Low portion patient-provided images. Conclusion: AD severity assessment based on images strongly correlates with in-person AD assessment. Good measurement properties confirm the potential of remote assessment. Moderate correlation between SA-EASI and in-person EASI suggest limited value of self-assessment.</p

Genome-wide association studies reveal QTL hotspots for grain brightness and black point traits in barley

Grain kernel discoloration (KD) in cereal crops leads to down-grading grain quality and substantial economic losses worldwide. Breeding KD tolerant varieties requires a clear understanding of the genetic basis underlying this trait. Here, we generated a high-density single nucleotide polymorphisms (SNPs) map for a diverse barley germplasm and collected trait data from two independent field trials for five KD related traits: grain brightness (TL), redness (Ta), yellowness (Tb), black point impact (Tbpi), and total black point in percentage (Tbpt). Although grain brightness and black point is genetically correlated, the grain brightness traits (TL, Ta, and Tb) have significantly higher heritability than that of the black point traits (Tbpt and Tbpi), suggesting black point traits may be more susceptible to environmental influence. Using genome-wide association studies (GWAS), we identified a total of 37 quantitative trait loci (QTL), including two major QTL hotspots on chromosomes 4H and 7H, respectively. The two QTL hotspots are associated with all five KD traits. Further genetic linkage and gene transcription analyses identified candidate genes for the grain KD, including several genes in the flavonoid pathway and plant peroxidase. Our study provides valuable insights into the genetic basis for the grain KD in barley and would greatly facilitate future breeding programs for improving grain KD resistance

Modeling electrolytically top gated graphene

We investigate doping of a single-layer graphene in the presence of electrolytic top gating. The interfacial phenomena is modeled using a modified Poisson-Boltzmann equation for an aqueous solution of simple salt. We demonstrate both the sensitivity of graphene's doping levels to the salt concentration and the importance of quantum capacitance that arises due to the smallness of the Debye screening length in the electrolyte.Comment: 7 pages, including 4 figures, submitted to Nanoscale Research Letters for a special issue related to the NGC 2009 conference (http://asdn.net/ngc2009/index.shtml

Text Line Segmentation of Historical Documents: a Survey

There is a huge amount of historical documents in libraries and in various National Archives that have not been exploited electronically. Although automatic reading of complete pages remains, in most cases, a long-term objective, tasks such as word spotting, text/image alignment, authentication and extraction of specific fields are in use today. For all these tasks, a major step is document segmentation into text lines. Because of the low quality and the complexity of these documents (background noise, artifacts due to aging, interfering lines),automatic text line segmentation remains an open research field. The objective of this paper is to present a survey of existing methods, developed during the last decade, and dedicated to documents of historical interest.Comment: 25 pages, submitted version, To appear in International Journal on Document Analysis and Recognition, On line version available at http://www.springerlink.com/content/k2813176280456k3

Identification of Novel Craniofacial Regulatory Domains Located far Upstream of SOX9 and Disrupted in Pierre Robin Sequence.

Mutations in the coding sequence of SOX9 cause campomelic dysplasia (CD), a disorder of skeletal development associated with 46,XY disorders of sex development (DSDs). Translocations, deletions, and duplications within a ∼2 Mb region upstream of SOX9 can recapitulate the CD-DSD phenotype fully or partially, suggesting the existence of an unusually large cis-regulatory control region. Pierre Robin sequence (PRS) is a craniofacial disorder that is frequently an endophenotype of CD and a locus for isolated PRS at ∼1.2-1.5 Mb upstream of SOX9 has been previously reported. The craniofacial regulatory potential within this locus, and within the greater genomic domain surrounding SOX9, remains poorly defined. We report two novel deletions upstream of SOX9 in families with PRS, allowing refinement of the regions harboring candidate craniofacial regulatory elements. In parallel, ChIP-Seq for p300 binding sites in mouse craniofacial tissue led to the identification of several novel craniofacial enhancers at the SOX9 locus, which were validated in transgenic reporter mice and zebrafish. Notably, some of the functionally validated elements fall within the PRS deletions. These studies suggest that multiple noncoding elements contribute to the craniofacial regulation of SOX9 expression, and that their disruption results in PRS

Tracking plasma DNA mutation dynamics in estrogen receptor positive metastatic breast cancer with dPCR-SEQ

Serial monitoring of plasma DNA mutations in estrogen receptor positive metastatic breast cancer (ER + MBC) holds promise as an early predictor of therapeutic response. Here, we developed dPCR-SEQ, a customized assay that utilizes digital PCR-based target enrichment followed by next-generation sequencing to analyze plasma DNA mutations in ESR1, PIK3CA, and TP53. We validated dPCR-SEQ in a prospective cohort of 58 patients with ER + MBC and demonstrate excellent concordance with hotspot ESR1 mutation abundance measured by conventional digital PCR. The dPCR-SEQ assay revealed ESR1, PIK3CA, and TP53 plasma ctDNA mutations in 55%, 32%, and 32% of the study patients, respectively. We also observed dynamic changes in ESR1, PIK3CA, and TP53 ctDNA mutant allele fraction (MAF) that were frequently discordant between the different genes. Thus, monitoring plasma DNA mutation dynamics using a dPCR-SEQ assay is feasible, accurate, and may be investigated as a biomarker of therapeutic response in ER + MBC

Ion-beam-induced reconstruction of amorphous GaN

Wurtzite GaN can be rendered amorphous by high-dose heavy-ion bombardment. We show here that relatively low-dose reirradiation of such amorphous GaN (a-GaN) with MeV light ions can significantly change some of the physical properties of a-GaN. In particular, light-ion reirradiation of a-GaN results in (i) an increase in material density, (ii) the suppression of complete decomposition during postimplantation annealing, (iii) a significant increase in the values of hardness and Young's modulus, and (iv) an apparent decrease in the absorption of visible light. Transmission electronmicroscopy shows that a-GaN remains completely amorphous after light-ion reirradiation. Therefore, we attribute the above effects of light-ion reirradiation to an ion-beam-induced atomic-level reconstruction of the amorphous phase. Results indicate that electronic energy loss of light ions is responsible for the changes in the mechanical properties and for the suppression of thermally induced decomposition of a-GaN. However, the changes in the density of a-GaN appear to be controlled by the nuclear energy loss of light ions

PIK3CA mutation in HPV-associated OPSCC patients receiving deintensified chemoradiation

PIK3CA is the most frequently mutated gene in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Prognostic implications of such mutations remain unknown. We sought to elucidate the clinical significance of PIK3CA mutations in HPV-associated OPSCC patients treated with definitive chemoradiation (CRT). Seventyseven patients with HPV-associated OPSCC were enrolled on two phase II clinical trials of deintensified CRT (60 Gy intensitymodulated radiotherapy with concurrent weekly cisplatin). Targeted next-generation sequencing was performed. Of the 77 patients, nine had disease recurrence (two regional, four distant, three regional and distant). Thirty-four patients had mutation( s) identified; 16 had PIK3CA mutations. Patients with wild-type-PIK3CA had statistically significantly higher 3-year disease-free survival than PIK3CA-mutant patients (93.4%, 95% confidence interval [CI] = 85.0% to 99.9% vs 68.8%, 95% CI = 26.7% to 89.8%; P=.004). On multivariate analysis, PIK3CA mutation was the only variable statistically significantly associated with disease recurrence (hazard ratio = 5.71, 95% CI = 1.53 to 21.3; P=.01). PIK3CA mutation is associated with worse diseasefree survival in a prospective cohort of newly diagnosed HPV-associated OPSCC patients treated with deintensified CRT

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.