A single sub-km Kuiper Belt object from a stellar Occultation in archival data

The Kuiper belt is a remnant of the primordial Solar System. Measurements of its size distribution constrain its accretion and collisional history, and the importance of material strength of Kuiper belt objects (KBOs). Small, sub-km sized, KBOs elude direct detection, but the signature of their occultations of background stars should be detectable. Observations at both optical and X-ray wavelengths claim to have detected such occultations, but their implied KBO abundances are inconsistent with each other and far exceed theoretical expectations. Here, we report an analysis of archival data that reveals an occultation by a body with a 500 m radius at a distance of 45 AU. The probability of this event to occur due to random statistical fluctuations within our data set is about 2%. Our survey yields a surface density of KBOs with radii larger than 250 m of 2.1^{+4.8}_{-1.7} x 10^7 deg^{-2}, ruling out inferred surface densities from previous claimed detections by more than 5 sigma. The fact that we detected only one event, firmly shows a deficit of sub-km sized KBOs compared to a population extrapolated from objects with r>50 km. This implies that sub-km sized KBOs are undergoing collisional erosion, just like debris disks observed around other stars.Comment: To appear in Nature on December 17, 2009. Under press embargo until 1800 hours London time on 16 December. 19 pages; 7 figure

Diagnostics and molecular epidemiology of the Sarcoptes scabiei mite infesting Australian wildlife

Parasitic infestations have always been a noteworthy topic for human and animal health globally, with many considered a result of spill-over and zoonosis. One such parasite, Sarcoptes scabiei, is known to infest over 300 million humans per year and has been documented in over 104 mammals. It has recently been classified as a neglected tropical disease and is among the top 50 most prevalent human diseases. With uncertainty over (i) the global epidemiology of S. scabiei and (ii) the reliability of current diagnostics methods, much still needs to be understood if stakeholders are to successfully develop strategies to control this parasite. The overall objective of this thesis was to study the molecular epidemiology and genetic typing of S. scabiei infesting Australian animals and assess the diagnostic methods for sarcoptic mange. At the global scale, numerous genetic studies have attempted to reveal how the host species and host geographic location influence S. scabiei phylogenetics. By performing an analysis of the global literature (Chapter 2), I was able to reveal that there were inconsistencies in gene loci and phylogenetic conclusions used in these previous studies. Furthermore, by executing a contemporary analytical approach employing molecular markers on existing S. scabiei sequences, it was apparent that (i) new S. scabiei samples, (ii) appropriate gene loci targets, and (iii) advanced phylogenetic approaches are necessary to more confidently comprehend the origins of mange in Australia. As there were only a limited number of Australian marsupial-derived S. scabiei sequences, and that three of the most commonly used gene loci used for typing are located within the mitochondria, I performed mitochondrial genome sequencing of mites collected from koalas and wombats (Chapter 3). It was revealed that there is a high sequence similarity not just within marsupial S. scabiei mites, but also to the only human-derived S. scabiei mitochondrial genome. Furthermore, by examining individual gene phylogenies, I concluded that cox1 is the most informative gene as the cox1 phylogeny inferred was consistent with the complete mitochondrial genome phylogeny with the highest resolution of ancestral lineages. Building on the identification of cox1 as an informative gene target, I greatly expanded the molecular typing of S. scabiei within Australia (Chapter 4). I identified that mites collected from koalas, wombats, foxes and dogs across five states of Australia were unable to be phylogenetically separated by their host or location. Thus, I considered it highly plausible that multiple spill-over events may have occurred in Australia, as many haplotypes are identical to European and non-European sequences. Furthermore, I suggested that it is likely that canids are the source for transmission of mange throughout Australian wildlife as dogs and foxes share identical haplotypes to wombats and koalas. Finally, I detected a distinguishable human-specific lineage, distinct from the dominant mixed animal clade. Clinical diagnosis of mange/scabies typically involves the collection of skin scrapings followed by microscopic detection of the mite. This method yields results with a high risk of false negatives, however. I performed the first comparative S. scabiei diagnostic study on a unique sample set collected from bare-nosed wombats. Here, I assessed a variety of putatively useful approaches including observational scoring, microscopy, PCR on skin scraping DNA and PCR on skin swab DNA (Chapter 5). I concluded that: (i) observational scoring positively correlated with counts from microscopy, however this approach tended to under-diagnose early mange; (ii) species-specific S. scabiei PCR enhanced the sensitivity of mite detection in relation to microscopy and; (iii) swabs as a method for sample collection is questionable due to inadequate host cell uptake and likelihood of producing false negatives. Finally, I sought to improve the use of molecular techniques for S. scabiei diagnosis (Chapter 6). I developed a novel rapid diagnostic tool using a Loop Mediated Isothermal Amplification assay, which I demonstrated to be specific to S. scabiei and able to produce a rapid diagnostic result within 30 minutes. Since this method can be performed without advanced laboratory equipment, this development has potential direct roles as an ancillary method with microscopy at the point-of-care to reduce the number of potential S. scabiei false-negative results obtained by microscopy alone in both human and veterinary settings. In summary, this thesis has contributed to: (i) the expansion of S. scabiei phylogeny by highlighting the high genetic variability of the single mite species; (ii) suggested multiple spill-over events may be the consequence of inadequate screening of imports/exports possibly globally and; (iii) has demonstrated the incompatible variety of different diagnostic methods for S. scabiei which may be supplemented with the development of a new highly sensitive and specific molecular technique. The contributions I have made in S. scabiei research will aid in future conservation efforts to aid in understanding transmission risks to threatened populations and enhance diagnostic procedures in clinical, field and remote settings

Meaning behind measurement : self-comparisons affect responses to health related quality of life questionnaires

Purpose The subjective nature of quality of life is particularly pertinent to the domain of health-related quality of life (HRQOL) research. The extent to which participants’ responses are affected by subjective information and personal reference frames is unknown. This study investigated how an elderly population living with a chronic metabolic bone disorder evaluated self-reported quality of life. Methods Participants (n = 1,331) in a multi-centre randomised controlled trial for the treatment of Paget’s disease completed annual HRQOL questionnaires, including the SF-36, EQ-5D and HAQ. Supplementary questions were added to reveal implicit reference frames used when making HRQOL evaluations. Twenty-one participants (11 male, 10 female, aged 59–91 years) were interviewed retrospectively about their responses to the supplementary questions, using cognitive interviewing techniques and semi-structured topic guides. Results The interviews revealed that participants used complex and interconnected reference frames to promote response shift when making quality of life evaluations. The choice of reference frame often reflected external factors unrelated to individual health. Many participants also stated that they were unclear whether to report general or disease-related HRQOL. Conclusions It is important, especially in clinical trials, to provide instructions clarifying whether ‘quality of life’ refers to disease-related HRQOL. Information on selfcomparison reference frames is necessary for the interpretation of responses to questions about HRQOL.The Chief Scientist Office of the Scottish Government Health Directorates, The PRISM funding bodies (the Arthritis Research Campaign, the National Association for the Relief of Paget’s disease and the Alliance for Better Bone Health)Peer reviewedAuthor final versio

Network Archaeology: Uncovering Ancient Networks from Present-day Interactions

Often questions arise about old or extinct networks. What proteins interacted in a long-extinct ancestor species of yeast? Who were the central players in the Last.fm social network 3 years ago? Our ability to answer such questions has been limited by the unavailability of past versions of networks. To overcome these limitations, we propose several algorithms for reconstructing a network's history of growth given only the network as it exists today and a generative model by which the network is believed to have evolved. Our likelihood-based method finds a probable previous state of the network by reversing the forward growth model. This approach retains node identities so that the history of individual nodes can be tracked. We apply these algorithms to uncover older, non-extant biological and social networks believed to have grown via several models, including duplication-mutation with complementarity, forest fire, and preferential attachment. Through experiments on both synthetic and real-world data, we find that our algorithms can estimate node arrival times, identify anchor nodes from which new nodes copy links, and can reveal significant features of networks that have long since disappeared.Comment: 16 pages, 10 figure

AXIOM: advanced X-ray imaging of the magnetosphere

Planetary plasma and magnetic field environments can be studied in two complementary ways—by in situ measurements, or by remote sensing. While the former provide precise information about plasma behaviour, instabilities and dynamics on local scales, the latter offers the global view necessary to understand the overall interaction of the magnetospheric plasma with the solar wind. Some parts of the Earth’s magnetosphere have been remotely sensed, but the majority remains unexplored by this type of measurements. Here we propose a novel and more elegant approach employing remote X-ray imaging techniques, which are now possible thanks to the relatively recent discovery of solar wind charge exchange X-ray emissions in the vicinity of the Earth’s magnetosphere. In this article we describe how an appropriately designed and located X-ray telescope, supported by simultaneous in situ measurements of the solar wind, can be used to image the dayside magnetosphere, magnetosheath and bow shock, with a temporal and spatial resolution sufficient to address several key outstanding questions concerning how the solar wind interacts with the Earth’s magnetosphere on a global level. Global images of the dayside magnetospheric boundaries require vantage points well outside the magnetosphere. Our studies have led us to propose ‘AXIOM: Advanced X-ray Imaging of the Magnetosphere’, a concept mission using a Vega launcher with a LISA Pathfinder-type Propulsion Module to place the spacecraft in a Lissajous orbit around the Earth–Moon L1 point. The model payload consists of an X-ray Wide Field Imager, capable of both imaging and spectroscopy, and an in situ plasma and magnetic field measurement package. This package comprises a Proton-Alpha Sensor, designed to measure the bulk properties of the solar wind, an Ion Composition Analyser, to characterise the minor ion populations in the solar wind that cause charge exchange emission, and a Magnetometer, designed to measure the strength and direction of the solar wind magnetic field. We also show simulations that demonstrate how the proposed X-ray telescope design is capable of imaging the predicted emission from the dayside magnetosphere with the sensitivity and cadence required to achieve the science goals of the mission

PhOTO Zebrafish: A Transgenic Resource for In Vivo Lineage Tracing during Development and Regeneration

Background: Elucidating the complex cell dynamics (divisions, movement, morphological changes, etc.) underlying embryonic development and adult tissue regeneration requires an efficient means to track cells with high fidelity in space and time. To satisfy this criterion, we developed a transgenic zebrafish line, called PhOTO, that allows photoconvertible optical tracking of nuclear and membrane dynamics in vivo. Methodology: PhOTO zebrafish ubiquitously express targeted blue fluorescent protein (FP) Cerulean and photoconvertible FP Dendra2 fusions, allowing for instantaneous, precise targeting and tracking of any number of cells using Dendra2 photoconversion while simultaneously monitoring global cell behavior and morphology. Expression persists through adulthood, making the PhOTO zebrafish an excellent tool for studying tissue regeneration: after tail fin amputation and photoconversion of a ~100µm stripe along the cut area, marked differences seen in how cells contribute to the new tissue give detailed insight into the dynamic process of regeneration. Photoconverted cells that contributed to the regenerate were separated into three distinct populations corresponding to the extent of cell division 7 days after amputation, and a subset of cells that divided the least were organized into an evenly spaced, linear orientation along the length of the newly regenerating fin. Conclusions/Significance: PhOTO zebrafish have wide applicability for lineage tracing at the systems-level in the early embryo as well as in the adult, making them ideal candidate tools for future research in development, traumatic injury and regeneration, cancer progression, and stem cell behavior

Zircon ages in granulite facies rocks: decoupling from geochemistry above 850 °C?

Granulite facies rocks frequently show a large spread in their zircon ages, the interpretation of which raises questions: Has the isotopic system been disturbed? By what process(es) and conditions did the alteration occur? Can the dates be regarded as real ages, reflecting several growth episodes? Furthermore, under some circumstances of (ultra-)high-temperature metamorphism, decoupling of zircon U–Pb dates from their trace element geochemistry has been reported. Understanding these processes is crucial to help interpret such dates in the context of the P–T history. Our study presents evidence for decoupling in zircon from the highest grade metapelites (> 850 °C) taken along a continuous high-temperature metamorphic field gradient in the Ivrea Zone (NW Italy). These rocks represent a well-characterised segment of Permian lower continental crust with a protracted high-temperature history. Cathodoluminescence images reveal that zircons in the mid-amphibolite facies preserve mainly detrital cores with narrow overgrowths. In the upper amphibolite and granulite facies, preserved detrital cores decrease and metamorphic zircon increases in quantity. Across all samples we document a sequence of four rim generations based on textures. U–Pb dates, Th/U ratios and Ti-in-zircon concentrations show an essentially continuous evolution with increasing metamorphic grade, except in the samples from the granulite facies, which display significant scatter in age and chemistry. We associate the observed decoupling of zircon systematics in high-grade non-metamict zircon with disturbance processes related to differences in behaviour of non-formula elements (i.e. Pb, Th, U, Ti) at high-temperature conditions, notably differences in compatibility within the crystal structure

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Deep and fast live imaging with two-photon scanned light-sheet microscopy

We implemented two-photon scanned light-sheet microscopy, combining nonlinear excitation with orthogonal illumination of light-sheet microscopy, and showed its excellent performance for in vivo, cellular-resolution, three-dimensional imaging of large biological samples. Live imaging of fruit fly and zebrafish embryos confirmed that the technique can be used to image up to twice deeper than with one-photon light-sheet microscopy and more than ten times faster than with point-scanning two-photon microscopy without compromising normal biology

Nano- and Micro-materials in the Treatment of Internal Bleeding and Uncontrolled Haemorrhage

Internal bleeding is defined as the loss of blood that occurs inside of a body cavity. After a traumatic injury, haemorrhage accounts for over 35% of pre-hospital deaths and 40% of deaths within the first 24hours. Coagulopathy, a disorder in which the blood is not able to properly form clots, typically develops after traumatic injury and results in a higher rate of mortality. The current methods to treat internal bleeding and coagulopathy are inadequate due to the requirement of extensive medical equipment that is typically not available at the site of injury. To discover a potential route for future research, several current and novel treatment methods have been reviewed and analysed. The aim of investigating different potential treatment options is to expand available knowledge, while also call attention to the importance of research in the field of treatment for internal bleeding and haemorrhage due to trauma