DECIPHER: Improving genetic diagnosis through dynamic integration of genomic and clinical data.

DECIPHER (Database of Genomic Variation and Phenotype in Humans Using Ensembl Resources) shares candidate diagnostic variants and phenotypic data from patients with genetic disorders to facilitate research and improve the diagnosis, management, and therapy of rare diseases. The platform sits at the boundary between genomic research and the clinical community. DECIPHER aims to ensure that the most up-to-date data are made rapidly available within its interpretation interfaces to improve clinical care. Newly integrated cardiac case-control data that provide evidence of gene-disease associations and inform variant interpretation exemplify this mission. New research resources are presented in a format optimized for use by a broad range of professionals supporting the delivery of genomic medicine. The interfaces within DECIPHER integrate and contextualize variant and phenotypic data, helping to determine a robust clinico-molecular diagnosis for rare-disease patients, which combines both variant classification and clinical fit. DECIPHER supports discovery research, connecting individuals within the rare-disease community to pursue hypothesis-driven research. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 24 is August 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates

Optimising subjective grading of corneal staining in Sjögren's syndrome dry eye disease

Aim: To assess whether smaller increment and regionalised subjective grading improves the repeatability of corneal fluorescein staining assessment, and to determine the neurological approach adopted for subjective grading by practitioners. Methods: Experienced eye-care practitioners (n = 28, aged 45 ± 12 years), graded 20 full corneal staining images of patients with mild to severe Sjögren's syndrome with the Oxford grading scheme (both in 0.5 and 1.0 increments, globally and in 5 regions), expanded National Eye Institute (NEI) and SICCA Ocular Staining Score (OSS) grading scales in randomised order. This was repeated after 7-10 days. The digital images were also analysed objectively to determine staining dots, area, intensity and location (using ImageJ) for comparison. Results: The Oxford grading scheme was similar with whole and half unit grading (2.77vs2.81,p = 0.145), but the variability was reduced (0.14vs0.12,p < 0.001). Regional grade was lower (p < 0.001) and more variable (p < 0.001) than global image grading (1.86 ± 0.44 for whole increment grading and 1.90 ± 0.39 for half unit increments). The correlation with global grading was high for both whole (r = 0.928,p < 0.001) and half increment (r = 0.934,p < 0.001) grading. Average grading across participants was associated with particle number and vertical position, with 74.4-80.4% of the linear variance accounted for by the digital image analysis. Conclusions: Using half unit increments with the Oxford grading scheme improve its sensitivity and repeatability in recording corneal staining. Regional grading doesn't give a comparable score and increased variability. The key neurally extracted features in assigning a subjective staining grade by clinicians were identified as the number of discrete staining locations (particles) and how close to the vertical centre was their spread, across all three scales

Reticulate evolution in Panicum (Poaceae): the origin of tetraploid broomcorn millet, P. miliaceum.

Panicum miliaceum (broomcorn millet) is a tetraploid cereal, which was among the first domesticated crops, but is now a minor crop despite its high water use efficiency. The ancestors of this species have not been determined; we aimed to identify likely candidates within the genus, where phylogenies are poorly resolved. Nuclear and chloroplast DNA sequences from P. miliaceum and a range of diploid and tetraploid relatives were used to develop phylogenies of the diploid and tetraploid species. Chromosomal in situ hybridization with genomic DNA as a probe was used to characterize the genomes in the tetraploid P. miliaceum and a tetraploid accession of P. repens. In situ hybridization showed that half the chromosomes of P. miliaceum hybridized more strongly with labelled genomic DNA from P. capillare, and half with labelled DNA from P. repens. Genomic DNA probes differentiated two sets of 18 chromosomes in the tetraploid P. repens. Our phylogenetic data support the allotetraploid origin of P. miliaceum, with the maternal ancestor being P. capillare (or a close relative) and the other genome being shared with P. repens. Our P. repens accession was also an allotetraploid with two dissimilar but closely related genomes, the maternal genome being similar to P. sumatrense. Further collection of Panicum species, particularly from the Old World, is required. It is important to identify why the water-efficient P. miliaceum is now of minimal importance in agriculture, and it may be valuable to exploit the diversity in this species and its ancestors

Adaptive memory: Stereotype activation is not enough

Studies have shown that survival processing leads to superior memorability. The aim of the present study was to examine whether this survival recall advantage might result from stereotype activation. To test this hypothesis, we conducted a pilot study and two experiments in which participants were primed with stereotypes (Experiment 1, professor and elderly person; Experiment 2, survival-stereotype). In Experiment 1, 120 undergraduates were randomly assigned to a survival, professor stereotype, elderly person stereotype, or moving scenario and rated words for their relevance to the imagined scenario. In Experiment 2, 75 undergraduates were given a survival, survival-stereotype (based on our pilot study), or moving scenario. Both experiments showed that survival processing leads to a greater recall advantage over the stereotype groups and control group. These data indicate that the mere activation of stereotypes cannot explain the survival recall advantage

Sex differences in mathematics and reading achievement are inversely related: within- and across-nation assessment of 10 years of PISA data

We analyzed one decade of data collected by the Programme for International Student Assessment (PISA), including the mathematics and reading performance of nearly 1.5 million 15 year olds in 75 countries. Across nations, boys scored higher than girls in mathematics, but lower than girls in reading. The sex difference in reading was three times as large as in mathematics. There was considerable variation in the extent of the sex differences between nations. There are countries without a sex difference in mathematics performance, and in some countries girls scored higher than boys. Boys scored lower in reading in all nations in all four PISA assessments (2000, 2003, 2006, 2009). Contrary to several previous studies, we found no evidence that the sex differences were related to nations’ gender equality indicators. Further, paradoxically, sex differences in mathematics were consistently and strongly inversely correlated with sex differences in reading: Countries with a smaller sex difference in mathematics had a larger sex difference in reading and vice versa. We demonstrate that this was not merely a between-nation, but also a within-nation effect. This effect is related to relative changes in these sex differences across the performance continuum: We did not find a sex difference in mathematics among the lowest performing students, but this is where the sex difference in reading was largest. In contrast, the sex difference in mathematics was largest among the higher performing students, and this is where the sex difference in reading was smallest. The implication is that if policy makers decide that changes in these sex differences are desired, different approaches will be needed to achieve this for reading and mathematics. Interventions that focus on high-achieving girls in mathematics and on low achieving boys in reading are likely to yield the strongest educational benefits

Relationships Among Self-Efficacy, Social Support, Social Problem Solving, and Self-Management in a Rural Sample Living With Type 2 Diabetes Mellitus

Self-management behaviors are important for control of type 2 diabetes mellitus. Therefore, determining factors that promote effective self-management behaviors may be significant for improving the well-being of patients with type 2 diabetes mellitus. This study examined relationships among self-efficacy, social support, social problem solving, and diabetes self-management behaviors. Further, this study evaluated whether social support and social problem solving were mediators of the relationship between self-efficacy and diabetes self-management behaviors in those living with type 2 diabetes mellitus. Using a cross-sectional, descriptive correlational design, data from a convenience sample of 152 rural people living with type 2 diabetes mellitus were examined. Findings indicated that self-efficacy was a strong predictor of diabetes self-management. The effect of social support on diabetes self-management differed among men and women in the sample. Social support and social problem solving were significantly associated with diabetes self-management in men. Neither social support nor social problem solving were mediators of the relationship between self-efficacy and diabetes self-management in this sample. These findings suggest that nurses need to consider implementing interventions to improve patients’ self-efficacy and potentially influence diabetes self-management

Turbulent ‘stopping plumes’ and plume pinch-off in uniform surroundings

Observations of turbulent convection in the environment are of variously sus- tained plume-like flows or intermittent thermal-like flows. At different times of the day the prevailing conditions may change and consequently the observed flow regimes may change. Understanding the link between these flows is of practical importance meteorologically, and here we focus our interest upon plume-like regimes that break up to form thermal-like regimes. It has been shown that when a plume rises from a boundary with low conductivity, such as arable land, the inability to maintain a rapid enough supply of buoyancy to the plume source can result in the turbulent base of the plume separating and rising away from the source. This plume ‘pinch-off’ marks the onset of the intermittent thermal-like behavior. The dynamics of turbulent plumes in a uniform environment are explored in order to investigate the phenomenon of plume pinch-off. The special case of a turbulent plume having its source completely removed, a ‘stopping plume’, is considered in particular. The effects of forcing a plume to pinch-off, by rapidly reducing the source buoyancy flux to zero, are shown experi- mentally. We release saline solution into a tank filled with fresh water generating downward propagating steady turbulent plumes. By rapidly closing the plume nozzle, the plumes are forced to pinch-off. The plumes are then observed to detach from the source and descend into the ambient. The unsteady buoyant region produced after pinch-off, cannot be described by the power-law behavior of either classical plumes or thermals, and so the terminology ‘stopping plume’ (analogous to a ‘starting plume’) is adopted for this type of flow. The propagation of the stopping plume is shown to be approximately linearly dependent on time, and we speculate therefore that the closure of the nozzle introduces some vorticity into the ambient, that may roll up to form a vortex ring dominating the dynamics of the base of a stopping plume

Quantum Acoustics with Surface Acoustic Waves

It has recently been demonstrated that surface acoustic waves (SAWs) can interact with superconducting qubits at the quantum level. SAW resonators in the GHz frequency range have also been found to have low loss at temperatures compatible with superconducting quantum circuits. These advances open up new possibilities to use the phonon degree of freedom to carry quantum information. In this paper, we give a description of the basic SAW components needed to develop quantum circuits, where propagating or localized SAW-phonons are used both to study basic physics and to manipulate quantum information. Using phonons instead of photons offers new possibilities which make these quantum acoustic circuits very interesting. We discuss general considerations for SAW experiments at the quantum level and describe experiments both with SAW resonators and with interaction between SAWs and a qubit. We also discuss several potential future developments.Comment: 14 pages, 12 figure

Ownership-dependent mating tactics of minor males of the beetle Librodor japonicus (Nitidulidae) with intra-sexual dimorphism of mandibles

Intra-sexual dimorphism is found in the weapons of many male beetles. Different behavioral tactics to access females between major and minor males, which adopt fighting and alternative tactics, respectively, are thought to maintain the male dimorphism. In these species major males have enlarged weapons that they use in fights with rival males. Minor males also have small weapons in some of these species, and it is unclear why these males possess weapons. We examined the hypothesis that minor males might adopt a fighting tactic when their status was relatively high in comparison with that of other males (e.g., ownership of a territory). We observed the behavioral tactics of major and minor males of the beetle Librodor japonicus, whose males have a dimorphism of their mandibles. Major males fought for resources, whereas minor males adopted two status-dependent tactics, fighting and sneaking, to access females, depending on their ownership of a sap site. We suggest that ownership status-dependent mating tactics in minor males may maintain the intra-sexual dimorphism in this beetle.</p

Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans

The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels of intra-specific sequence variation and a lack of reference genomes, makes their assembly and annotation a challenging task. Haemonchus contortus is an economically significant parasite of livestock that is widely used for basic research as well as for vaccine development and drug discovery. It is one of many medically and economically important parasites within the strongylid nematode group. This group of parasites has the closest phylogenetic relationship with the model organism Caenorhabditis elegans, making comparative analysis a potentially powerful tool for genome annotation and functional studies. To investigate this hypothesis, we sequenced two contiguous fragments from the H. contortus genome and undertook detailed annotation and comparative analysis with C. elegans. The adult H. contortus transcriptome was sequenced using an Illumina platform and RNA-seq was used to annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a 181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative transposable elements were identified. 97.5% of the annotated genes had detectable homologues in C. elegans of which 60% had putative orthologues, significantly higher than previous analyses based on EST analysis. Gene density appears to be less in H. contortus than in C. elegans, with annotated H. contortus genes being an average of two-to-three times larger than their putative C. elegans orthologues due to a greater intron number and size. Synteny appears high but gene order is generally poorly conserved, although areas of conserved microsynteny are apparent. C. elegans operons appear to be partially conserved in H. contortus. Our findings suggest that a combination of RNA-seq and comparative analysis with C. elegans is a powerful approach for the annotation and analysis of strongylid nematode genomes