3,138 research outputs found

    Effective health care for older people resident in care homes: the optimal study protocol for realist review

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    This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Care homes in the UK rely on general practice for access to specialist medical and nursing care as well as referral to therapists and secondary care. Service delivery to care homes is highly variable in both quantity and quality. This variability is also evident in the commissioning and organisation of care home-specific services that range from the payment of incentives to general practitioners (GPs) to visit care homes, to the creation of care home specialist teams and outreach services run by geriatricians. No primary studies or systematic reviews have robustly evaluated the impact of these different approaches on organisation and resident-level outcomes. Our aim is to identify factors which may explain the perceived or demonstrated effectiveness of programmes to improve health-related outcomes in older people living in care homes. Methods/Design: A realist review approach will be used to develop a theoretical understanding of what works when, why and in what circumstances. Elements of service models of interest include those that focus on assessment and management of residents’ health, those that use strategies to encourage closer working between visiting health care providers and care home staff, and those that address system-wide issues about access to assessment and treatment. These will include studies on continence, dignity, and speech and language assessment as well as interventions to promote person centred dementia care, improve strength and mobility, and nutrition. The impact of these interventions and their different mechanisms will be considered in relation to five key outcomes: residents’ medication use, use of out of hours’ services, hospital admissions (including use of Accident and Emergency) and length of hospital stay, costs and user satisfaction. An iterative three-stage approach will be undertaken that is stakeholder-driven and optimises the knowledge and networks of the research team. Discussion: This realist review will explore why and for whom different approaches to providing health care to residents in care homes improves access to health care in the five areas of interest. It will inform commissioning decisions and be the basis for further research. This systematic review protocol is registered on the PROSPERO database reference number: CRD42014009112NIHR Health Services & Delivery Research Programme. Project number 11/1021/0

    Fission yeast 26S proteasome mutants are multi-drug resistant due to stabilization of the pap1 transcription factor

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    Here we report the result of a genetic screen for mutants resistant to the microtubule poison methyl benzimidazol-2-yl carbamate (MBC) that were also temperature sensitive for growth. In total the isolated mutants were distributed in ten complementation groups. Cloning experiments revealed that most of the mutants were in essential genes encoding various 26S proteasome subunits. We found that the proteasome mutants are multi-drug resistant due to stabilization of the stress-activated transcription factor Pap1. We show that the ubiquitylation and ultimately the degradation of Pap1 depend on the Rhp6/Ubc2 E2 ubiquitin conjugating enzyme and the Ubr1 E3 ubiquitin-protein ligase. Accordingly, mutants lacking Rhp6 or Ubr1 display drug-resistant phenotypes

    Characterization of Shewanella oneidensis MtrC: a cell-surface decaheme cytochrome involved in respiratory electron transport to extracellular electron acceptors

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    MtrC is a decaheme c-type cytochrome associated with the outer cell membrane of Fe(III)-respiring species of the Shewanella genus. It is proposed to play a role in anaerobic respiration by mediating electron transfer to extracellular mineral oxides that can serve as terminal electron acceptors. The present work presents the first spectropotentiometric and voltammetric characterization of MtrC, using protein purified from Shewanella oneidensis MR-1. Potentiometric titrations, monitored by UV–vis absorption and electron paramagnetic resonance (EPR) spectroscopy, reveal that the hemes within MtrC titrate over a broad potential range spanning between approximately +100 and approximately -500 mV (vs. the standard hydrogen electrode). Across this potential window the UV–vis absorption spectra are characteristic of low-spin c-type hemes and the EPR spectra reveal broad, complex features that suggest the presence of magnetically spin-coupled low-spin c-hemes. Non-catalytic protein film voltammetry of MtrC demonstrates reversible electrochemistry over a potential window similar to that disclosed spectroscopically. The voltammetry also allows definition of kinetic properties of MtrC in direct electron exchange with a solid electrode surface and during reduction of a model Fe(III) substrate. Taken together, the data provide quantitative information on the potential domain in which MtrC can operate

    The role of Comprehension in Requirements and Implications for Use Case Descriptions

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    Within requirements engineering it is generally accepted that in writing specifications (or indeed any requirements phase document), one attempts to produce an artefact which will be simple to comprehend for the user. That is, whether the document is intended for customers to validate requirements, or engineers to understand what the design must deliver, comprehension is an important goal for the author. Indeed, advice on producing ‘readable’ or ‘understandable’ documents is often included in courses on requirements engineering. However, few researchers, particularly within the software engineering domain, have attempted either to define or to understand the nature of comprehension and it’s implications for guidance on the production of quality requirements. Therefore, this paper examines thoroughly the nature of textual comprehension, drawing heavily from research in discourse process, and suggests some implications for requirements (and other) software documentation. In essence, we find that the guidance on writing requirements, often prevalent within software engineering, may be based upon assumptions which are an oversimplification of the nature of comprehension. Hence, the paper examines guidelines which have been proposed, in this case for use case descriptions, and the extent to which they agree with discourse process theory; before suggesting refinements to the guidelines which attempt to utilise lessons learned from our richer understanding of the underlying discourse process theory. For example, we suggest subtly different sets of writing guidelines for the different tasks of requirements, specification and design

    Rossby wave dynamics of the North Pacific extra-tropical response to El Niño: importance of the basic state in coupled GCMs

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    The extra-tropical response to El Nino in a "low" horizontal resolution coupled climate model, typical of the Intergovernmental Panel on Climate Change fourth assessment report simulations, is shown to have serious systematic errors. A high resolution configuration of the same model has a much improved response that is similar to observations. The errors in the low resolution model are traced to an incorrect representation of the atmospheric teleconnection mechanism that controls the extra-tropical sea surface temperatures (SSTs) during El Nino. This is due to an unrealistic atmospheric mean state, which changes the propagation characteristics of Rossby waves. These erroneous upper tropospheric circulation anomalies then induce erroneous surface circulation features over the North Pacific. The associated surface wind speed and direction errors create erroneous surface flux and upwelling anomalies which finally lead to the incorrect extra-tropical SST response to El Nino in the low resolution model. This highlights the sensitivity of the climate response to a single link in a chain of complex climatic processes. The correct representation of these processes in the high resolution model indicates the importance of horizontal resolution in resolving such processes

    The exoskeletons are here

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    It is a fantastic time for the field of robotic exoskeletons. Recent advances in actuators, sensors, materials, batteries, and computer processors have given new hope to creating the exoskeletons of yesteryear's science fiction. While the most common goal of an exoskeleton is to provide superhuman strength or endurance, scientists and engineers around the world are building exoskeletons with a wide range of diverse purposes. Exoskeletons can help patients with neurological disabilities improve their motor performance by providing task specific practice. Exoskeletons can help physiologists better understand how the human body works by providing a novel experimental perturbation. Exoskeletons can even help power mobile phones, music players, and other portable electronic devices by siphoning mechanical work performed during human locomotion. This special thematic series on robotic lower limb exoskeletons and orthoses includes eight papers presenting novel contributions to the field. The collective message of the papers is that robotic exoskeletons will contribute in many ways to the future benefit of humankind, and that future is not that distant

    The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes

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    To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance

    ALG: Automated Genotype Calling of Luminex Assays

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    Single nucleotide polymorphisms (SNPs) are the most commonly used polymorphic markers in genetics studies. Among the different platforms for SNP genotyping, Luminex is one of the less exploited mainly due to the lack of a robust (semi-automated and replicable) freely available genotype calling software. Here we describe a clustering algorithm that provides automated SNP calls for Luminex genotyping assays. We genotyped 3 SNPs in a cohort of 330 childhood leukemia patients, 200 parents of patient and 325 healthy individuals and used the Automated Luminex Genotyping (ALG) algorithm for SNP calling. ALG genotypes were called twice to test for reproducibility and were compared to sequencing data to test for accuracy. Globally, this analysis demonstrates the accuracy (99.6%) of the method, its reproducibility (99.8%) and the low level of no genotyping calls (3.4%). The high efficiency of the method proves that ALG is a suitable alternative to the current commercial software. ALG is semi-automated, and provides numerical measures of confidence for each SNP called, as well as an effective graphical plot. Moreover ALG can be used either through a graphical user interface, requiring no specific informatics knowledge, or through command line with access to the open source code. The ALG software has been implemented in R and is freely available for non-commercial use either at http://alg.sourceforge.net or by request to [email protected]
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