Genetic variation within the Daphnia pulex genome

Genetic variation within the diploid Daphnia pulex genome was examined using a high quality de novo assembly and shotgun reads from two distinct D. pulex clones. Patterns of variation and divergence at single nucleotides were examined in physical and functional regions of the genome using comparative assembly output and available annotations. Additionally, mitochondrial genomes of the same D. pulex clones were assembled and compared for patterns of divergence, and substitutional biases. Intron presence/absence polymorphisms were identified computationally and verified experimentally. Finally, gene duplicate demographics were examined for patterns of divergence and estimates of gene birth rates

Understanding implementation success: protocol for an in-depth, mixed-methods process evaluation of a cluster randomised controlled trial testing methods to improve detection of Lynch syndrome in Australian hospitals.

INTRODUCTION:In multisite intervention trials, implementation success often varies widely across settings. Process evaluations are crucial to interpreting trial outcomes and understanding contextual factors and causal chains necessary for successful implementation. Lynch syndrome is a hereditary cancer predisposition conferring an increased risk of colorectal, endometrial and other cancer types. Despite systematic screening protocols to identify Lynch syndrome, the condition remains largely underdiagnosed. The Hide and Seek Project ('HaSP') is a cluster randomised controlled trial determining the effectiveness of two approaches to improving Lynch syndrome detection at eight Australian hospital networks. To enhance widespread implementation of optimal Lynch syndrome identification, there is a need to understand not only what works, but also why, in what contexts, and at what costs. Here we describe an in-depth investigation of factors influencing successful implementation of procedures evaluated in the HaSP trial. METHODS AND ANALYSIS:A mixed-methods, theory-driven process evaluation will be undertaken in parallel to the HaSP trial. Data will include: interviews of Implementation Leads and Lynch syndrome stakeholders, pre-post implementation questionnaires, audio analysis of meetings and focus groups, observation of multidisciplinary team meetings, fidelity checklists and project log analysis. Results will be triangulated and coded, drawing on the Theoretical Domains Framework, Consolidated Framework for Implementation Research and Proctor's implementation outcomes. ETHICS AND DISSEMINATION:Use of a theory-based process evaluation will enhance interpretation and generalisability of HaSP trial findings, and contribute to the implementation research field by furthering understanding of the conditions necessary for implementation success. Ethical approval has been granted and results will be disseminated via publications in peer-reviewed journals and conference presentations. At trial completion, key findings will be fed back to sites to enable refinement of intervention strategies, both in the context of Lynch syndrome and for the possible generalisability of intervention components in other genetic and broader clinical specialties. HASP TRIAL REGISTRATION NUMBER:Australian New Zealand Clinical Trials Registry (Identifier: ACTRN12618001072202). Registered 27 June 2018. http://www.ANZCTR.org.au/ACTRN12618001072202.aspx

Relativistic Elastostatics I: Bodies in Rigid Rotation

We consider elastic bodies in rigid rotation, both nonrelativistically and in special relativity. Assuming a body to be in its natural state in the absence of rotation, we prove the existence of solutions to the elastic field equations for small angular velocity.Comment: 25 page

Extensive error in the number of genes inferred from draft genome assemblies

Current sequencing methods produce large amounts of data, but genome assemblies based on these data are often woefully incomplete. These incomplete and error-filled assemblies result in many annotation errors, especially in the number of genes present in a genome. In this paper we investigate the magnitude of the problem, both in terms of total gene number and the number of copies of genes in specific families. To do this, we compare multiple draft assemblies against higher-quality versions of the same genomes, using several new assemblies of the chicken genome based on both traditional and next-generation sequencing technologies, as well as published draft assemblies of chimpanzee. We find that upwards of 40% of all gene families are inferred to have the wrong number of genes in draft assemblies, and that these incorrect assemblies both add and subtract genes. Using simulated genome assemblies of Drosophila melanogaster, we find that the major cause of increased gene numbers in draft genomes is the fragmentation of genes onto multiple individual contigs. Finally, we demonstrate the usefulness of RNA-Seq in improving the gene annotation of draft assemblies, largely by connecting genes that have been fragmented in the assembly process

The Sloan Bright Arcs Survey : Six Strongly Lensed Galaxies at z=0.4-1.4

We present new results of our program to systematically search for strongly lensed galaxies in the Sloan Digital Sky Survey (SDSS) imaging data. In this study six strong lens systems are presented which we have confirmed with follow-up spectroscopy and imaging using the 3.5m telescope at the Apache Point Observatory. Preliminary mass models indicate that the lenses are group-scale systems with velocity dispersions ranging from 466-878 km s^{-1} at z=0.17-0.45 which are strongly lensing source galaxies at z=0.4-1.4. Galaxy groups are a relatively new mass scale just beginning to be probed with strong lensing. Our sample of lenses roughly doubles the confirmed number of group-scale lenses in the SDSS and complements ongoing strong lens searches in other imaging surveys such as the CFHTLS (Cabanac et al 2007). As our arcs were discovered in the SDSS imaging data they are all bright ($r\lesssim22$), making them ideally suited for detailed follow-up studies.Comment: 13 pages, 3 figures, submitted to ApJL, the Sloan Bright Arcs page is located here: http://home.fnal.gov/~kubo/brightarcs.htm

Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration

Acknowledgements We are indebted to Jim Humphries, JennyCorrigan, LizDarley, Elizabeth Joynson, Natalie Walters, Sara Wells and the whole necropsy, histology, genotyping and MLC ward 6 teams at MRC Harwell for excellent technical assistance. We thank the staff of the WTSI Illumina Bespoke Team for the RNA-seq data, the Sanger Mouse Genetics Project for the initial mouse characterization and Dr David Adams for critical reading of the manuscript. We also thank KOMP for the mouse embryonic stem cells carrying the knockout first promoter-less allele (tm1a(KOMP)Wtsi) within Zfp016. Conflict of Interest statement. None declared. Funding This work was funded by the UK Medical Research Council (MRC) to A.A.-A. and a Motor Neurone Disease Association (MNDA) project grant to A.A.-A. and EMCF. D.L.H.B. is a Wellcome Trust Senior Clinical Scientist Fellow and P.F. is a MRC/MNDA Lady Edith Wolfson Clinician Scientist Fellow. Funding to pay the Open Access publication charges for this article was provided by the MRC grant number: MC_UP_A390_1106.Peer reviewedPublisher PD

Differences in Clinical and Functional Outcomes Between Osteochondral Allograft Transplantation and Autologous Chondrocyte Implantation when Used in the Treatment of Focal Grade 3 and Grade 4 Articular Cartilage Defects

Introduction: Grade 3 and 4 articular cartilage defects involve 50% of cartilage thickness without involvement of the underlying bone. There are several available options for the surgical repair of articular cartilage lesions including osteochondral allograft transplantation (OCA), a well-established procedure, and autologous chondrocyte implantation (ACI), an alternative developed more recently. Although there are studies examining ACI outcomes, there hasn’t been significant comparison of ACI outcomes to other procedures, including OCA. The inquiry question of this study was: how do clinical and functional outcomes differ between patients with focal articular cartilage defects treated with ACI and patients treated with OCA? Methods: After IRB approval, a database query identified patients who had undergone ACI or OCA between 2008 and 2016. Eligible patients were contacted via telephone and/or email to complete functional outcome surveys including the Knee injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR.), International Knee Documentation Committee (IKDC), and the 12-Item Short Form (SF-12). A retrospective chart review was performed to obtain demographic information as well as information related to ACI and OCA. Statistical analysis was performed using a combination of a Fischer’s exact or chi-squared test, Mann-Whitney U test, and Kruskal-Wallis test, using a statistical significance value of P \u3c 0.05. Results: The patient cohort was composed of 89 (50.6%) patients who had undergone ACI and 87 (49.4%) patients who had undergone OCA. The ACI group compared to the OCA group had a lower mean KOOS, JR. score (72.65 ± 16.93 vs 73.95 ± 18.91, p = 0.634), lower IKDC score (61.91 ± 21.12 vs 63.92 ± 22.55, p = 0.544), and higher SF-12 score (49.16 ± 7.46 vs 47.81 ± 9.61, p = 0.312) although none of the differences were statistically significant. Within the ACI group, no patients required revision surgery although 5 (5.6%) patients underwent total knee arthroplasty or OCA due to persistence of symptoms. Within the OCA group, 5 (5.7%) patients required revision surgery, while 7 (8.0%) patients underwent an additional procedure due to failure. A total of 16 (18.3%) patients, including 2 patients who underwent revision OCA, required conversion to total or unicompartmental arthroplasty, additional OCA procedure unrelated to previous OCA failure, or ACI due to persistence of symptoms. The rate of failure, defined as the need for revision or subsequent surgery to resolve symptoms, was significantly greater in the OCA group (25.3% vs 5.6%, p \u3c 0.001). Discussion: The results of this study indicate that patients who underwent ACI for articular cartilage defects had statistically similar functional outcomes (KOOS, JR., IDKC, SF-12 scores) as patients who underwent OCA. However, the ACI group demonstrated a lower rate of failure compared to the OCA group. These findings may indicate a preference for ACI over OCA for the repair of grade 3 and 4 articular cartilage lesions in order to reduce the rate of subsequent surgeries and/or failure

Differences in Clinical and Functional Outcomes Between Osteochondral Allograft Transplantation and Autologous Chondrocyte Implantation for the Treatment of Focal Articular Cartilage Defects

Background: Articular cartilage pathology can result from a spectrum of origins, including trauma, osteochondritis dissecans, avascular necrosis, or degenerative joint disease. Purpose: To compare the differences in clinical and patient-reported outcomes after autologous chondrocyte implantation (ACI) versus osteochondral allograft transplantation (OCA) in patients with focal articular cartilage defects without underlying bone loss. Study design: Cohort study; Level of evidence, 3. Methods: A retrospective review identified patients who underwent ACI or OCA between 2008 and 2016 for isolated grades 3 and 4 articular cartilage defects without underlying bone loss. Outcome measures included the Knee injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR), International Knee Documentation Committee (IKDC) evaluation, and 12-Item Short Form Health Survey-Physical Component (SF-12-P) scores. Defect location, size, complications, and rate of subsequent surgery were determined. Results: Overall, 148 patients were included: 82 (55%) underwent ACI and 66 (45%) underwent OCA. The mean age at the time of surgery was 31.2 years within the ACI cohort and 37.7 years within the OCA cohort (P \u3c .001); the mean follow-up for both cohorts was 6.7 years (P = .902). Within the ACI group, 28 (34%) patients had multifocal defects, 21 (26%) had defects confined to the femoral condyles, and 33 (40%) had defects in the patellofemoral region. Within the OCA group, 23 (35%) patients had multifocal defects, 30 (46%) had confined femoral condyle lesions, and 13 (20%) had patellofemoral defects. When comparing by lesion location, there were no significant differences in KOOS JR, and IKDC scores between the ACI and OCA cohorts (P \u3c .05). There was, however, a significant difference for SF-12-P scores for FDD trochlear lesions. In both cohorts, traumatic patellofemoral pathology demonstrated lower patient-reported outcomes and higher failure rates than degenerative lesions. The overall rate of failure, defined as graft failure with revision surgery and/or conversion to arthroplasty, was significantly greater in the OCA group (21% vs 4%; P = .002). Conclusion: Study results indicated that ACI provides similar outcomes to OCA with or without concomitant procedures for the treatment of symptomatic articular cartilage defects in all lesion locations and may have a lower revision rate for multifocal and condylar lesions

The Norris Survey of the Corona Borealis Supercluster: II. Galaxy Evolution with Redshift and Environment

We measure the field galaxy luminosity function (LF) as a function of color and redshift from z = 0 to z = 0.5 using galaxies from the Norris Survey of the Corona Borealis Supercluster. We find that our local r-band LF, when normalized to counts in high galactic latitude fields, agrees well with the local LF measured in the Las Campanas Redshift Survey. Our B-band local LF, however, does not match the B-band LF from the Stromlo/APM survey, having a normalization 1.6 times higher. We see compelling evidence that B-band field galaxy LF evolves with redshift. The evolution is strongest for the population of star-forming galaxies with [OII]3727 rest-frame equivalent widths greater than 10A. The population of red, quiescent galaxies shows no sign of evolution to z = 0.5. The evolution of the LF which we observe is consistent with the findings of other faint galaxy redshift surveys. The fraction of galaxies with [OII] emission increases rapidly with redshift, but the fraction of galaxies with strong Hdelta 4101 absorption, a signature of a burst of star formation, does not. We thus conclude that the star formation in distant galaxies is primarily long-lived. We also compute the LFs of the Corona Borealis supercluster and the A2069 supercluster. The shapes of the two supercluster LFs are broadly similar to the shape of the local LF. However, there are important differences. Both supercluster LFs have an excess of very bright galaxies. In addition, there is a suggestion of an upturn in the LF for galaxies fainter than M(B) = -17 mag. (Abridged from the abstract in the paper.)Comment: 28 pages plus 18 pages of figures; accepted for publication in Ap

Measuring and Modelling the Redshift Evolution of Clustering: the Hubble Deep Field North

(abridged) The evolution of galaxy clustering from z=0 to z=4.5 is analyzed using the angular correlation function and the photometric redshift distribution of galaxies brighter than I_{AB}\le 28.5 in the HDF North. The reliability of the photometric redshift estimates is discussed on the basis of the available spectroscopic redshifts, comparing different codes and investigating the effects of photometric errors. The redshift bins in which the clustering properties are measured are then optimized to take into account the uncertainties of the photometric redshifts. The results show that the comoving correlation length has a small decrease in the range 0<z<1 followed by an increase at higher z. We compare these results with the theoretical predictions of a variety of cosmological models belonging to the general class of CDM. The comparison with the expected mass clustering evolution indicates that the observed high-redshift galaxies are biased tracers of the dark matter with an effective bias b strongly increasing with redshift. Assuming an Einstein-de Sitter universe, we obtain b\simeq 2 at z=2 and b\simeq 5 at z=4. A comparison of the clustering amplitudes that we measured at z=3 with those reported for LBG suggests that the clustering depends on the abundance of the objects: more abundant objects are less clustered, as expected in the paradigm of hierarchical galaxy formation. The strong clustering and high bias measured at z=3 are consistent with the expected density of massive haloes predicted for the various cosmologies here considered. At z=4, the strong clustering observed in the HDF requires a significant fraction of massive haloes to be already formed by that epoch. This feature could be a discriminant test for the cosmological parameters if confirmed by future observations.Comment: 23 pages, Latex using MN style, figures enclosed. Version accepted for publication in MNRA