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Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium.
A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing.
Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects.
In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.
The science of studying diamond inclusions for understanding Earth history has developed significantly over the past decades, with new instrumentation and techniques applied to diamond sample archives revealing the stories contained within diamond inclusions. This chapter reviews what diamonds can tell us about the deep carbon cycle over the course of Earth’s history. It reviews how the geochemistry of diamonds and their inclusions inform us about the deep carbon cycle, the origin of the diamonds in Earth’s mantle, and the evolution of diamonds through time.
To develop consensus recommendations for training future clinician educators (CEs) in emergency medicine (EM).
A panel of EM education leaders was assembled from across Canada and met regularly by teleconference over the course of 1 year. Recommendations for CE training were drafted based on the panel’s experience, a literature review, and a survey of current and past EM education leaders in Canada. Feedback was sought from attendees at the Canadian Association of Emergency Physicians (CAEP) annual academic symposium. Recommendations were distributed to the society’s Academic Section for further feedback and updated by a consensus of the expert panel.
Recommendations were categorized for one of three audiences: 1) Future CEs; 2) Academic departments and divisions (AD&D) that support training to fulfill their education leadership goals; and 3) The CAEP Academic Section. Advanced medical education training is recommended for any emergency physician or resident who pursues an education leadership role. Individuals should seek out mentorship in making decisions about career opportunities and training options. AD&D should regularly perform a needs assessment of their future CE needs and identify and encourage potential individuals who fulfill education leadership roles. AD&D should develop training opportunities at their institution, provide support to complete this training, and advocate for the recognition of education scholarship in their institutional promotions process. The CAEP Academic Section should support mentorship of future CEs on a national scale.
These recommendations serve as a framework for training and supporting the next generation of Canadian EM medical educators.
Coupling is considered between fluid flow and a freely moving body shorter than the development length in an oncoming boundary layer or channel flow but longer than the flow thickness. The body lies within the core of the flow. The coupling occurs between the inviscid-dominated displacement and the viscous–inviscid pressure, the latter acting to move the body. This interaction can be unstable. It is found however that three factors serve to stabilise the interaction as each one alters the decisive balance of angular momentum. One is a 10 % shift forward in the position of the centre of mass. The second is a degree of flexibility in the body shape by means of its response to the induced pressure force. Third is a slight streamwise movement of the body which is sufficient to modify the viscous–inviscid pressure response and again produce stabilisation. The effects are largely independent of the lateral position of the body.
The glycaemic and insulin indices assess postprandial glycaemic and insulin response to foods, respectively, which may not reflect the long-term effects of diet on insulin response. We developed and evaluated the validity of four empirical indices to assess the insulinaemic potential of usual diets and lifestyles, using dietary, lifestyle and biomarker data from the Nurses’ Health Study (NHS, n 5812 for hyperinsulinaemia, n 3929 for insulin resistance). The four indices were as follows: the empirical dietary index for hyperinsulinaemia (EDIH) and the empirical lifestyle index for hyperinsulinaemia (ELIH); the empirical dietary index for insulin resistance (EDIR) and the empirical lifestyle index for insulin resistance (ELIR). We entered thirty-nine FFQ-derived food groups in stepwise linear regression models, and defined indices as patterns most predictive of fasting plasma C-peptide, for the hyperinsulinaemia pathway (EDIH and ELIH), and of theTAG:HDL-cholesterol ratio, for the insulin-resistance pathway (EDIR and ELIR). We evaluated the validity of indices in two independent samples from NHS-II and Health Professionals Follow-up Study (HPFS) using multivariable-adjusted linear regression analyses to calculate relative concentrations of biomarkers. The EDIH is comprised of eighteen food groups; thirteen were positively associated with C-peptide and five were inversely associated. The EDIR is comprised of eighteen food groups; ten were positively associated with TAG:HDL-cholesterol and eight were inversely associated. Lifestyle indices had fewer dietary components, and included BMI and physical activity as components. In the validation samples, all indices significantly predicted biomarker concentrations – for example, the relative concentrations of the corresponding biomarkers comparing extreme index quintiles in the HPFS were EDIH, 1·29 (95 % CI 1·22, 1·37); ELIH, 1·78 (95 % CI 1·68, 1·88); EDIR, 1·44 (95 % CI 1·34, 1·55); and ELIR, 2·03 (95 % CI 1·89, 2·19); all Ptrend<0·0001. The robust associations of these novel hypothesis-driven indices with insulin response biomarker concentrations suggest their usefulness in assessing the ability of whole diets and lifestyles to stimulate and/or sustain insulin secretion.
The objective of this study was to determine the economic value of obtaining timely and more accurate clinical mastitis (CM) test results for optimal treatment of cows. Typically CM is first identified when the farmer observes recognisable outward signs. Further information of whether the pathogen causing CM is Gram-positive, Gram-negative or other (including no growth) can be determined by using on-farm culture methods. The most detailed level of information for mastitis diagnostics is obtainable by sending milk samples for culture to an external laboratory. Knowing the exact pathogen permits the treatment method to be specifically targeted to the causation pathogen, resulting in less discarded milk. The disadvantages are the additional waiting time to receive test results, which delays treating cows, and the cost of the culture test. Net returns per year (NR) for various levels of information were estimated using a dynamic programming model. The Value of Information (VOI) was then calculated as the difference in NR using a specific level of information as compared to more detailed information on the CM causative agent. The highest VOI was observed where the farmer assumed the pathogen causing CM was the one with the highest incidence in the herd and no pathogen specific CM information was obtained. The VOI of pathogen specific information, compared with non-optimal treatment of Staphylococcus aureus where recurrence and spread occurred due to lack of treatment efficacy, was $20.43 when the same incorrect treatment was applied to recurrent cases, and $30.52 when recurrent cases were assumed to be the next highest incidence pathogen and treated accordingly. This indicates that negative consequences associated with choosing the wrong CM treatment can make additional information cost-effective if pathogen identification is assessed at the generic information level and if the pathogen can spread to other cows if not treated appropriately.
Complex biological products, such as those used to treat various forms of cancer, are typically produced by mammalian cells in bioreactors. The most important class of such biological medicines is proteins. These typically bind to sugars (glycans) in a process known as glycosylation, creating glycoproteins, which are more stable and effective medicines. The glycans are large polymers that are formed by a long sequence of enzyme catalysed reactions. This sequence is not always completed, thus leading to a heterogeneous glycoprotein distribution. A better comprehension of this distribution could lead to more efficient production of high quality drugs. To understand how the manufacturing process can affect the extent of glycosylation of protein, a non-linear ODE model of glycoprotein production is developed which describes the bioreactor configuration as well as the protein production and glycosylation reactions within the cell. The entire system evolves eventually to a stable steady state. The earlier evolution is critical however, as the amount of product produced and its quality varies over time. The model is considered as two coupled systems: the bioreactor submodel and the glycosylation submodel. To investigate the early time evolution within the bioreactor submodel, analytical and numerical properties are derived using matched asymptotic expansions and a finite difference scheme for a range of initial conditions. This leads to qualitatively different regimes for aglycosylated protein production, which affect the glycosylation submodel. The discrete glycoprotein distribution is approximated as continuous and written as a first-order PDE, with good agreement between the discrete and continuous models. The PDE is found to admit shocks, but the existence of these shocks is dependent on the early time evolution within the bioreactor submodel and leads to higher levels of glycosylation at early time. This suggests that changing the bioreactor configuration can lead to higher quality product at certain times.
Fluid motion at high Reynolds number over a flexible in-wall blip (a compliant bump or dip in an otherwise fixed wall) is considered theoretically for a very short blip buried low inside a boundary layer. Only the near-wall shear of the oncoming flow affects the local motion past the tiny blip. Slowly evolving features are examined first to allow for variations in the incident flow. Linear and nonlinear solutions show that at certain parameter values (eigenvalues) intensifications occur in which the interactive effect on flow and blip shape is larger by an order of magnitude than at most parameter values. Similar findings apply to the boundary layer with several tiny blips present or to channel flows with blips of almost any length. These intensifications lead on to fully nonlinear unsteady motion as a second stage, after some delay, thus combining with finite-time breakups to form a distinct path into transition of the flow.
Obesity is a growing problem in India, the dietary determinants of which have been studied using an ‘individual food/nutrient’ approach. Examining dietary patterns may provide more coherent findings, but few studies in developing countries have adopted this approach. The present study aimed to identify dietary patterns in an Indian population and assess their relationship with anthropometric risk factors.
FFQ data from the cross-sectional sib-pair Indian Migration Study (IMS; n 7067) were used to identify dietary patterns using principal component analysis. Mixed-effects logistic regression was used to examine associations with obesity and central obesity.
The IMS was conducted at four factory locations across India: Lucknow, Nagpur, Hyderabad and Bangalore.
The participants were rural-to-urban migrant and urban non-migrant factory workers, their rural and urban resident siblings, and their co-resident spouses.
Three dietary patterns were identified: ‘cereals–savoury foods’ (cooked grains, rice/rice-based dishes, snacks, condiments, soups, nuts), ‘fruit–veg–sweets–snacks’ (Western cereals, vegetables, fruit, fruit juices, cooked milk products, snacks, sugars, sweets) and ‘animal-food’ (red meat, poultry, fish/seafood, eggs). In adjusted analysis, positive graded associations were found between the ‘animal-food’ pattern and both anthropometric risk factors. Moderate intake of the ‘cereals–savoury foods’ pattern was associated with reduced odds of obesity and central obesity.
Distinct dietary patterns were identified in a large Indian sample, which were different from those identified in previous literature. A clear ‘plant food-based/animal food-based pattern’ dichotomy emerged, with the latter being associated with higher odds of anthropometric risk factors. Longitudinal studies are needed to further clarify this relationship in India.
Conditions are investigated under which a body lying at rest or rocking on a solid horizontal surface can be removed from the surface by hydrodynamic forces or instead continues rocking. The investigation is motivated by recent observations on Martian dust movement as well as other small- and large-scale applications. The nonlinear theory of fluid–body interaction here has unsteady motion of an inviscid fluid interacting with a moving thin body. Various shapes of body are addressed together with a range of initial conditions. The relevant parameter space is found to be subtle as evolution and shape play substantial roles coupled with scaled mass and gravity effects. Lift-off of the body from the surface generally cannot occur without fluid flow but it can occur either immediately or within a finite time once the fluid flow starts up: parameters for this are found and comparisons are made with Martian observations.
Significant new opportunities for astrophysics and cosmology have been identified at low radio frequencies. The Murchison Widefield Array is the first telescope in the southern hemisphere designed specifically to explore the low-frequency astronomical sky between 80 and 300 MHz with arcminute angular resolution and high survey efficiency. The telescope will enable new advances along four key science themes, including searching for redshifted 21-cm emission from the EoR in the early Universe; Galactic and extragalactic all-sky southern hemisphere surveys; time-domain astrophysics; and solar, heliospheric, and ionospheric science and space weather. The Murchison Widefield Array is located in Western Australia at the site of the planned Square Kilometre Array (SKA) low-band telescope and is the only low-frequency SKA precursor facility. In this paper, we review the performance properties of the Murchison Widefield Array and describe its primary scientific objectives.
Digital signal processing is one of many valuable tools for suppressing unwanted signals or inter-ference. Building hardware processing engines seems to be the way to best implement some classes of interference suppression but is, unfortunately, expensive and time-consuming, especially if several miti-gation techniques need to be compared. Simulations can be useful, but are not a substitute for real data. CSIRO’s Australia Telescope National Facility has recently commenced a ‘software radio telescope’ project designed to fill the gap between dedicated hardware processors and pure simulation. In this approach, real telescope data are recorded coherently, then processed offline. This paper summarises the current contents of a freely available database of base band recorded data that can be used to experiment with signal processing solutions. It includes data from the following systems: single dish, multi-feed receiver; single dish with reference antenna; and an array of six 22 m antennas with and without a reference antenna. Astronomical sources such as OH masers, pulsars and continuum sources subject to interfering signals were recorded. The interfering signals include signals from the US Global Positioning System (GPS) and its Russian equivalent (GLONASS), television, microwave links, a low-Earth-orbit satellite, various other transmitters, and signals leaking from local telescope systems with fast clocks. The data are available on compact disk, allowing use in general purpose computers or as input to laboratory hardware prototypes.