1,548 research outputs found

    Probabilistic models to describe the dynamics of migrating microbial communities

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    In all but the most sterile environments bacteria will reside in fluid being transported through conduits and some of these will attach and grow as biofilms on the conduit walls. The concentration and diversity of bacteria in the fluid at the point of delivery will be a mix of those when it entered the conduit and those that have become entrained into the flow due to seeding from biofilms. Examples include fluids through conduits such as drinking water pipe networks, endotracheal tubes, catheters and ventilation systems. Here we present two probabilistic models to describe changes in the composition of bulk fluid microbial communities as they are transported through a conduit whilst exposed to biofilm communities. The first (discrete) model simulates absolute numbers of individual cells, whereas the other (continuous) model simulates the relative abundance of taxa in the bulk fluid. The discrete model is founded on a birth-death process whereby the community changes one individual at a time and the numbers of cells in the system can vary. The continuous model is a stochastic differential equation derived from the discrete model and can also accommodate changes in the carrying capacity of the bulk fluid. These models provide a novel Lagrangian framework to investigate and predict the dynamics of migrating microbial communities. In this paper we compare the two models, discuss their merits, possible applications and present simulation results in the context of drinking water distribution systems. Our results provide novel insight into the effects of stochastic dynamics on the composition of non-stationary microbial communities that are exposed to biofilms and provides a new avenue for modelling microbial dynamics in systems where fluids are being transported

    Concise Review: Stem Cell Therapies for Amyotrophic Lateral Sclerosis: Recent Advances and Prospects for the Future

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    Amyotrophic lateral sclerosis (ALS) is a lethal disease involving the loss of motor neurons. Although the mechanisms responsible for motor neuron degeneration in ALS remain elusive, the development of stem cell‐based therapies for the treatment of ALS has gained widespread support. Here, we review the types of stem cells being considered for therapeutic applications in ALS, and emphasize recent preclinical advances that provide supportive rationale for clinical translation. We also discuss early trials from around the world translating cellular therapies to ALS patients, and offer important considerations for future clinical trial design. Although clinical translation is still in its infancy, and additional insight into the mechanisms underlying therapeutic efficacy and the establishment of long‐term safety are required, these studies represent an important first step toward the development of effective cellular therapies for the treatment of ALS. S tem C ells 2014;32:1099–1109Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106861/1/stem1628.pd

    Distributed expertise: Qualitative study of a British network of multidisciplinary teams supporting parents of children with chronic kidney disease

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    © 2014 The Authors. Background: Long-term childhood conditions are often managed by hospital-based multidisciplinary teams (MDTs) of professionals with discipline specific expertise of a condition, in partnership with parents. However, little evidence exists on professional-parent interactions in this context. An exploration of professionals' accounts of the way they individually and collectively teach parents to manage their child's clinical care at home is, therefore, important for meeting parents' needs, informing policy and educating novice professionals. Using chronic kidney disease as an exemplar this paper reports on one aspect of a study of interactions between professionals and parents in a network of 12 children's kidney units in Britain. Methods: We conducted semi-structured, qualitative interviews with a convenience sample of 112 professionals (clinical-psychologists, dietitians, doctors, nurses, pharmacists, play-workers, therapists and social workers), exploring accounts of their parent-educative activity. We analysed data using framework and the concept of distributed expertise. Results: Four themes emerged that related to the way expertise was distributed within and across teams: (i) recognizing each other's' expertise, (ii) sharing expertise within the MDT, (iii) language interpretation, and (iv) acting as brokers. Two different professional identifications were also seen to co-exist within MDTs, with participants using the term 'we' both as the intra-professional 'we' (relating to the professional identity) when describing expertise within a disciplinary group (for example: 'As dietitians we aim to give tailored advice to optimize children's growth'), and the inter-professional 'we' (a 'team-identification'), when discussing expertise within the team (for example: 'We work as a team and make sure we're all happy with every aspect of their training before they go home'). Conclusions: This study highlights the dual identifications implicit in 'being professional' in this context (to the team and to one's profession) as well as the unique role that each member of a team contributes to children's care. Our methodology and results have the potential to be transferred to teams managing other conditions

    Stem cell technology for neurodegenerative diseases

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    Over the past 20 years, stem cell technologies have become an increasingly attractive option to investigate and treat neurodegenerative diseases. In the current review, we discuss the process of extending basic stem cell research into translational therapies for patients suffering from neurodegenerative diseases. We begin with a discussion of the burden of these diseases on society, emphasizing the need for increased attention toward advancing stem cell therapies. We then explain the various types of stem cells utilized in neurodegenerative disease research, and outline important issues to consider in the transition of stem cell therapy from bench to bedside. Finally, we detail the current progress regarding the applications of stem cell therapies to specific neurodegenerative diseases, focusing on Parkinson disease, Huntington disease, Alzheimer disease, amyotrophic lateral sclerosis, and spinal muscular atrophy. With a greater understanding of the capacity of stem cell technologies, there is growing public hope that stem cell therapies will continue to progress into realistic and efficacious treatments for neurodegenerative diseases. Ann Neurol 2011;70: 353–361.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86937/1/22487_ftp.pd

    An Investigation into Gender Disparities in the Field of Computing

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    This paper explains the reasons as to why there is under-representation of females computer science. Recent research undertaken at a British University focused on gender imbalance amongst academic staff in the Faculty of Technology and Environment, Liverpool John Moores University. The paper presents evidence that suggests the significance of identifying female role models in the field as a precursor to improving the current gender imbalance amongst academic faculty. In addition, the paper suggests the importance of addressing the negative stereotypical images related to the discipline and suggests the importance of identifying barriers to access and mobility females encounter in the field. The results of this initial investigation demonstrate the subjective belief amongst female academic faculty that in the School of Computing is dominated by male academics. Further, this belief pattern manifests itself in a perceived lack of motivation for promotion in the School. It can be concluded that the deeply entrenched belief system determines a lack of attempts to seek and secure promotion amongst all grades of female faculty. The paper proposes recommendations which the School could adopt to improve recruitment and retention of female academic staff and students

    Autocrine Production of IGF‐I Increases Stem Cell‐Mediated Neuroprotection

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    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder resulting in motor neuron (MN) loss. There are currently no effective therapies; however, cellular therapies using neural progenitor cells protect MNs and attenuate disease progression in G93A‐SOD1 ALS rats. Recently, we completed a phase I clinical trial examining intraspinal human spinal stem cell (HSSC) transplantation in ALS patients which demonstrated our approach was safe and feasible, supporting the phase II trial currently in progress. In parallel, efforts focused on understanding the mechanisms underlying the preclinical benefit of HSSCs in vitro and in animal models of ALS led us to investigate how insulin‐like growth factor‐I (IGF‐I) production contributes to cellular therapy neuroprotection. IGF‐I is a potent growth factor with proven efficacy in preclinical ALS studies, and we contend that autocrine IGF‐I production may enhance the salutary effects of HSSCs. By comparing the biological properties of HSSCs to HSSCs expressing sixfold higher levels of IGF‐I, we demonstrate that IGF‐I production augments the production of glial‐derived neurotrophic factor and accelerates neurite outgrowth without adversely affecting HSSC proliferation or terminal differentiation. Furthermore, we demonstrate that increased IGF‐I induces more potent MN protection from excitotoxicity via both indirect and direct mechanisms, as demonstrated using hanging inserts with primary MNs or by culturing with organotypic spinal cord slices, respectively. These findings support our theory that combining autocrine growth factor production with HSSC transplantation may offer a novel means to achieve additive neuroprotection in ALS. Stem Cells 2015;33:1480–1489Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111155/1/stem1933.pd

    Secondary school pupils' preferences for different types of structured grouping practices

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    The aim of this paper is to explore pupils’ preferences for particular types of grouping practices an area neglected in earlier research focusing on the personal and social outcomes of ability grouping. The sample comprised over 5,000 year 9 pupils (aged 13-14 years) in 45 mixed secondary comprehensive schools in England. The schools represented three levels of ability grouping in the lower school (years 7 to 9). Pupils responded to a questionnaire which explored the types of grouping that they preferred and the reasons for their choices. The majority of pupils preferred setting, although this was mediated by their set placement, type of school, socio-economic status and gender. The key reason given for this preference was that it enabled work to be matched to learning needs. The paper considers whether there are other ways of achieving this avoiding the negative social and personal outcomes of setting for some pupils

    Do intraplate and plate boundary fault systems evolve in a similar way with repeated slip events?

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    As repeated slip events occur on a fault, energy is partly dissipated through rock fracturing and frictional processes in the fault zone and partly radiated to the surface as seismic energy. Numerous field studies have shown that the core of intraplate faults is wider on average with increasing total displacement (and hence slip events). In this study we compile data on the fault core thickness, total displacement and internal structure (e.g., fault core composition, host rock juxtaposition, slip direction, fault type, and/or the number of fault core strands) of plate boundary faults to compare to intraplate faults (within the interior of tectonic plates). Fault core thickness data show that plate boundary faults are anomalously narrow by comparison to intraplate faults and that they remain narrow regardless of how much total displacement they have experienced or the local structure of the fault. By examining the scaling relations between seismic moment, average displacement and surface rupture length for plate boundary and intraplate fault ruptures, we find that for a given value of displacement in an individual earthquake, plate boundary fault earthquakes typically have a greater seismic moment (and hence earthquake magnitude) than intraplate events. We infer that narrow plate boundary faults do not process intact rock as much during seismic events as intraplate faults. Thus, plate boundary faults dissipate less energy than intraplate faults during earthquakes meaning that for a given value of average displacement, more energy is radiated to the surface manifested as higher magnitude earthquakes. By contrast, intraplate faults dissipate more energy and get wider as fault slip increases, generating complex zones of damage in the surrounding rock and propagating through linkage with neighbouring structures. The more complex the fault geometry, the more energy has to be consumed at depth during an earthquake and the less energy reaches the surface

    Transformation and patterning of supermicelles using dynamic holographic assembly

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    Although the solution self-assembly of block copolymers has enabled the fabrication of a broad range of complex, functional nanostructures, their precise manipulation and patterning remain a key challenge. Here we demonstrate that spherical and linear supermicelles, supramolecular structures held together by non-covalent solvophobic and coordination interactions and formed by the hierarchical self-assembly of block copolymer micelle and block comicelle precursors, can be manipulated, transformed and patterned with mediation by dynamic holographic assembly (optical tweezers). This allows the creation of new and stable soft-matter superstructures far from equilibrium. For example, individual spherical supermicelles can be optically held in close proximity and photocrosslinked through controlled coronal chemistry to generate linear oligomeric arrays. The use of optical tweezers also enables the directed deposition and immobilization of supermicelles on surfaces, allowing the precise creation of arrays of soft-matter nano-objects with potentially diverse functionality and a range of applications
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