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Ribosome profiling (also known as Ribo-seq) has become an important technique to investigate changes in translation across a wide variety of contexts. Ribo-seq data not only provides the abundance of ribosomes bound to transcripts, but also positional information across transcripts that could be indicative of differences in translation dynamics between conditions. While many computational tools exist for the analysis of Ribo-seq data, including those that assess differences in translational efficiency between conditions, no tool currently exists for rigorous test of the pattern differences in ribosome footprint. In this paper we propose a novel approach together with an R package, RiboDiPA, for Differential PPattern Analysis of Ribo-seq data. RiboDiPA allows for quick identification of genes with statistically significant differences in ribosome occupancy patterns for model organisms ranging from yeast to mammals. We show that differential pattern analysis reveals information that is distinct and complimentary to the existing methods that focus on translational efficiency analysis. Using both simulated Ribo-seq footprint data and two benchmark data sets, we illustrate that RiboDiPA can not only uncover meaningful global translational differences between conditions, but also the detailed differential ribosome binding patterns to a single codon resolution.

Lower limb trauma is the most common injury sustained in motorcycle crashes. There are limited data describing this cohort in Australia and limited international data establishing costs due to lower limb trauma following motorcycle crashes.This retrospective cohort study utilised administrative hospitalisation data from Queensland, Australia from 2011-2017. Eligible participants included those admitted with a principal diagnosis coded as lower extremity or pelvic fracture following a motorcycle crash (defined as the index admission). Multiply injured motorcyclists where the lower limb injury was not coded as the primary diagnosis (i.e. principal diagnosis was rather coded as head injury, internal organ injures etc.) were not included in the study. Hospitalisation data were also linked to clinical costing data. Logistic regression was used to determine risk factors for 30-day readmission. Costing data were compared between those readmitted and those who weren't, using bootstrapped t-tests and ANVOA.A total of 3342 patients met eligibility, with the most common lower limb fracture being tibia/fibula fractures (40.8%). 212 participants (6.3%) were readmitted within 30-days of discharge. The following were found to predict readmission: male sex (OR 1.84, 95% CI 1.01-1.94); chronic anaemia (OR 2.19, 95% CI 1.41-3.39); current/ex-smoker (OR 1.60, 95% CI 1.21-2.12); emergency admission (OR 2.77, 95% CI 1.35-5.70) and tibia/fibula fracture type (OR 1.46, 95% CI 1.10-1.94). The most common reasons for readmission were related to ongoing fracture care, infection or post-operative complications. The average hospitalisation cost for the index admission was AU$29,044 (95% CI $27,235-$30,853) with significant differences seen between fracture types. The total hospitalisation cost of readmissions was almost AU$2 million over the study period, with an average cost of $10,977 (95% CI $9,131- $13,059).Unplanned readmissions occur in 6.3% of lower limb fractures sustained in motorcycle crashes. Independent predictors of readmission within 30 days of discharge included male sex, chronic anaemia, smoking status, fracture type and emergency admission. Index admission and readmission hospitalisation costs are substantial and should prompt health services to invest in ways to reduce readmission.

Background The use of smartphones and multimedia messaging service (MMS) continues to increase in day to day orthopaedic clinical practice. However, there is limited evidence to support the safe utilisation of MMS. Objectives The aim of this study was to correlate the performance of MMS imaging to picture archiving and communication systems (PACS) imaging within the setting of diagnosis and management of ankle fractures. Methods The ankle fracture radiograph series of 82 consecutive patients were evaluated by five orthopaedic consultant specialists. A questionnaire regarding diagnosis and preferred management was completed separately for each patient using smartphone and PACS images. Statistical analysis was performed using Intraclass Correlation Coefficient (ICC). Results Ankle fracture diagnosis showed strong to excellent correlation both inter- and intraobserver MMS vs PACS when using the Weber (0.815, 0.988), Anatomical (0.858, 0.988), and AO classification systems (0.855, 0.985). MMS was less reliable than PACS in determining many management options. Conclusion The reliability of ankle fracture classification using MMS image viewing was not significantly different to interpretation on PACS workstations. Smartphone use in ankle fracture classification is supported by this study. Smartphone use was less accurate than PACS in devising management plans and future use should be limited to making only initial plans that must be corroberated with PACS and intraoperative findings prior to definitive fixation.

Transcription factors use both protein-DNA and protein-protein interactions to assemble appropriate complexes to regulate gene expression. Although most transcription factors operate as monomers or dimers, a few, including the E26 transformation-specific family repressors Drosophila melanogaster Yan and its human homolog TEL/ETV6, can polymerize. Although polymerization is required for both the normal and oncogenic function of Yan and TEL/ETV6, the mechanisms by which it influences the recruitment, organization, and stability of transcriptional complexes remain poorly understood. Further, a quantitative description of the DNA occupancy of a polymerizing transcription factor is lacking, and such a description would have broader applications to the conceptually related area of polymerizing chromatin regulators. To expand the theoretical basis for understanding how the oligomeric state of a transcriptional regulator influences its chromatin occupancy and function, we leveraged the extensive biochemical characterization of E26 transformation-specific factors to develop a mathematical model of Yan occupancy at chemical equilibrium. We find that spreading condensation from a specific binding site can take place in a path-independent manner given reasonable values of the free energies of specific and non-specific DNA binding and protein-protein cooperativity. Our calculations show that polymerization confers upon a transcription factor the unique ability to extend occupancy across DNA regions far from specific binding sites. In contrast, dimerization promotes recruitment to clustered binding sites and maximizes discrimination between specific and non-specific sites. We speculate that the association with non-specific DNA afforded by polymerization may enable regulatory behaviors that are well-suited to transcriptional repressors but perhaps incompatible with precise activation.

The discovery of the Atlantida Cu–Au–Mo porphyry deposit, which is unconformably overlain by 25–80 m of gravels, is a recent example of exploration success under cover in a traditional mining jurisdiction. Early acquisition of geophysics was a key tool in the discovery, and in later guiding further exploration drilling throughout the life of the project. Detailed review of the geophysical response of the deposit, with respect to the distribution of lithologies and alteration, coupled with their petrophysical properties has allowed full characterisation, despite no exposure at the surface of host rock nor porphyry-style mineralisation. Data acquired over the project include induced polarisation, magnetotellurics, ground and airborne magnetics, ground-based gravimetry, and petrophysical sampling. The distribution of the key geological features of the deposit has been inferred via acquisition of petrophysical properties and interpretation of surface geophysical datasets. Magnetic susceptibility is influenced strongly by both alteration and primary lithology, whilst density variations are dominated by primary lithological control. Several studies have shown that electrical properties may map the footprint of the hydrothermal system and associated mineralisation, via a combination of chargeability and resistivity. These properties are observed in geophysical datasets acquired at surface and allow further targeting and sterilisation at the deposit and project scale. By understanding these geophysical characteristics in a geological context, these data can be used to infer distribution of lithological units, depth to exploration targets and the potential for high grade mineralisation. Future exploration will likely be increasingly reliant on the understanding of the surface manifestations of buried deposits in remotely acquired data. This review summarises the application and results of these principles at the Atlantida project of northern Chile. Geophysical data can be used to improve the chances of discovery beneath post-mineral cover, and also improve drilling results throughout the advanced exploration of the program. The process of data review against geological control information is essential.

IntroductionAnkle fractures are common in the elderly population. Surgical fixation is technically challenging and often results in complications due to high rates of osteoporosis and vascular disease. Open reduction and internal fixation (ORIF) often requires prolonged periods of non-weight bearing increasing the risks of complications. Tibiotalocalcaneal (TTC) nailing has been suggested as an alternative to ORIF which allows immediate weight bearing, and is suggested to result in fewer complications. This study aims to compare the two surgical techniques in the elderly population with ankle fractures.Methods and analysisThe study will be a multicentre, prospective, randomised controlled trial comparing ORIF to TTC nailing in 110 patients with ankle fractures aged 50 or above with a Charlson Comorbidity Index of greater than or equal to four. Participants and assessors will not be blinded to intervention. The primary outcome measure will be overall complication rate. Secondary outcomes include length of hospital stay, mobility at discharge, discharge destination, the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot score, the Olerud-Molander Ankle Score, mortality rate, rate of secondary surgical interventions and number of blood transfusions required postoperatively. Our null hypothesis is that there is no clinically significant difference in the primary outcome measure between the two treatment groups.Ethics and disseminationThe study has been approved by Metro South Hospital and Health Services Human Research Ethics Committee (EC00167) (reference number HREC/17/QPAH/351).DiscussionCompletion of this trial will provide evidence on the effectiveness of TTC nailing versus ORIF in treatment of the elderly ankle fracture. If TTC nailing is found to result in superior outcomes, this trial has the capacity to change current clinical practice.Trial registration numberACTRN12617001588381;Pre-results andU1111-1203-1704.

During development, transcriptional complexes at enhancers regulate gene expression in complex spatiotemporal patterns. To achieve robust expression without spurious activation, the affinity and specificity of transcription factor–DNA interactions must be precisely balanced. Protein–protein interactions among transcription factors are also critical, yet how their affinities impact enhancer output is not understood. The Drosophila transcription factor Yan provides a well-suited model to address this, as its function depends on the coordinated activities of two independent and essential domains: the DNA-binding ETS domain and the self-associating SAM domain. To explore how protein–protein affinity influences Yan function, we engineered mutants that increase SAM affinity over four orders of magnitude. This produced a dramatic subcellular redistribution of Yan into punctate structures, reduced repressive output and compromised survival. Cell-type specification and genetic interaction defects suggest distinct requirements for polymerization in different regulatory decisions. We conclude that tuned protein–protein interactions enable the dynamic spectrum of complexes that are required for proper regulation.

The discovery of the Atlantida Cu-Au-Mo porphyry deposit is a recent example of exploration success under cover in a traditional mining jurisdiction. Early and appropriate acquisition of geophysics...

Light-inducible dimerization tags are engineered to rapidly recruit proteins to precise points in living yeast and mammalian cells. The affinities and response time of the interactions are tunable, and the authors used the system to activate cell signaling and to direct cell polarization in yeast. Naturally photoswitchable proteins offer a means of directly manipulating the formation of protein complexes that drive a diversity of cellular processes. We developed tunable light-inducible dimerization tags (TULIPs) based on a synthetic interaction between the LOV2 domain of Avena sativa phototropin 1 (AsLOV2) and an engineered PDZ domain (ePDZ). TULIPs can recruit proteins to diverse structures in living yeast and mammalian cells, either globally or with precise spatial control using a steerable laser. The equilibrium binding and kinetic parameters of the interaction are tunable by mutation, making TULIPs readily adaptable to signaling pathways with varying sensitivities and response times. We demonstrate the utility of TULIPs by conferring light sensitivity to functionally distinct components of the yeast mating pathway and by directing the site of cell polarization.

Direct targeting of mineral deposits using magnetic data may be facilitated by hydrothermal alteration associated with the mineralising event if the alteration changes the magnetic properties of the host rock. Hydrothermal alteration associated with porphyry-style mineralisation typically comprises concentric near-circular alteration zones surrounding a roughly circular central intrusion. The intrusion itself and the proximal alteration zone are usually associated with positive magnetic anomalies whilst the outer alteration zones are much less magnetic. Because the country rocks are usually magnetic, this pattern of alteration produces a central magnetic ‘high’ surrounded by an annular magnetic ‘low’. This paper presents an automatic image analysis system for gridded data that provides an efficient, accurate and non-subjective way to seek the magnetic response of an idealised porphyry mineralising system within magnetic datasets. The method finds circular anomalies that are associated with the central intrusion and inner alteration zone of the porphyry system using a circular feature detection method called the radial symmetry transform. Next, their boundaries are traced using deformable splines that are drawn to the locations of maximum contrast between the amplitudes of the central ‘high’ and surrounding area of lower magnetisation. Experiments were conducted on magnetic data from Reko Diq, Pakistan; a region known to contain numerous occurrences of porphyry-style mineralisation. The predicted locations of porphyry systems closely match the locations of the known deposits in this region. This system is suitable as an initial screening tool for large geophysical datasets, therefore reducing the time and cost imposed by manual data inspection in the exploration process. The same principles can be applied to the search for circular magnetic responses with different amplitude characteristics.

Background: The standard treatment for a non-union of the hallux metatarsophalangeal joint fusion has been to revise the fusion. Revision fusion is technically more demanding, often involving bone grafting, more substantial fixation and prolonged period of immobilization postoperatively. We present data to suggest that removal of hardware and debridement alone is an alternative treatment option. Materials and Methods: A case note review identified patients with a symptomatic non-union after hallux metatarsophalangeal joint (MTPJ) fusion. It is our practice to offer these patients revision fusion or removal of hardware and debridement. For the seven patients that chose hardware removal and were left with a pseudarthrosis, a matched control group was selected from patients who had had successful fusions. Three outcome scores were used. Hallux valgus and dorsiflexion angles were recorded. Results: One hundred thirty-nine hallux MTPJ arthrodeses were carried out. Fourteen non-unions were identified. The rate of nonunion in males and following previous hallux MTPJ surgery was 19% and 24%, respectively. In females undergoing a primary MTPJ fusion, the rate was 2.4%. Twelve non-union patients were reviewed at 27 months (mean). Eleven patients had elected to undergo removal of hardware and debridement. Four patients with pseudarthrosis were unhappy with the results and proceeded to either revision fusion or MTPJ replacement. Seven non-union patients, who had removal of hardware alone, had outcome scores marginally worse compared to those with successful fusions. Conclusion: Removal of hardware alone is a reasonable option to offer as a relatively minor procedure following a failed arthrodesis of the first MTPJ. This must be accepted on the proviso that in this study four out of 11 (36%) patients proceeded to a revision first MTPJ fusion or first MTPJ replacement. We also found that the rate of non-union in primary first MTPJ fusion was significantly higher in males and those patients who had undergone previous surgery. Level of Evidence: III, Retrospective Comparative Series

GEM Beijing 2011: International Workshop on Gravity, Electrical & Magnetic Methods and Their Applications Beijing, China. October 10-13, 2011. Automated detection of responses from porphyry-style mineralisation within magnetic data Eun-Jung Holden, Shih-Ching Fu, Peter Kovesi, Mike Dentith, Matthew Hope, Barry Bourne Centre for Exploration Targeting, School of Earth & Environment, The University of Western Australia, Crawley, Western Australia, Australia ** Barrick Gold of Australia, Perth, Western Australia, Australia *** Barrick Gold Exploration Inc., Elko, Nevada, United States of America

An understanding of the processes of tendon healing and tendon-to-bone healing is important for the intraoperative and postoperative management of patients with tendon ruptures or of patients requiring tendon transfers in foot and ankle surgery. Knowledge of the normal process allows clinicians to develop strategies when normal healing fails. This article reviews the important work behind the identification of the normal phases and control of tendon healing. It outlines the failed response in tendinopathy and describes tendon-to-bone healing in view of its importance in foot and ankle surgery.