117 research outputs found
AN APPROACH FOR THE DEVELOPMENT OF COMPUTER BASED BEST PRACTICE DELIVERY MECHANISMS FOR SMALL AND MEDIUM SIZED MANUFACTURING ENTERPRISES
Changes in the competitive environment have strongly influenced manufacturing companies
to adopt and develop best practice. Best practice is usually imported into companies using
the services of consultancy organisations. The use of consultancy services does not
guarantee success however, and inadequate results have been obtained by practitioners who
have engaged in client-consultant relationships. The inadequacy of these results may be
explained by the installation of pre-defined solutions by consultants as opposed to the
adaptation and implementation of solutions to meet the specific requirements of
practitioners. Tills may in part be explained by a lack of understanding of 'best practice'.
Tills work presented in this thesis investigated the feasibility of computer based mechanisms
for intervention in small and medium sized enterprises (SMEs) for the delivery of best
practice. The research was undertaken using a prototyping approach. Three prototype
computer based tools (CBTs) were developed by the author and tested by practitioners. The
prototypes were designed based on a set of objectives and a framework of features which
was developed. These frameworks were constructed from a synthesis of the research
findings which included a study of best practice, the identification of characteristics of types
of intervention, the identification of SME characteristics, and inhibitors of change in SMEs.
The research has indicated that an approach using computer based tools is appropriate for
intervention in SMEs and for adapting best practice to meet specific requirements. A
structured project management approach is required with identifiable goals and benefits. An
exploratory learning environment should be used to deliver complex best practice concepts
and to support the goal oriented approach. Tools and techniques provided by the CBT
enable the achievement of methodological tasks and facilitate experimentation and learning.
The approach should not prescribe solutions, but should provide information through
computer generated analyses to support decision making. The research suggests that the
proposed approach may support a workbook based methodology, or may encapsulate a
process methodology.
The originality of this work is in the provision of a definition of best practice, an explanation
of the deficiencies of existing mechanisms for the transfer of best practice to SMEs, and the
specification of the features required by a new computer-based approach. Tills provides new
knowledge for the field of production and operations management
Preliminary Cost Model for Space Telescopes
Parametric cost models are routinely used to plan missions, compare concepts and justify technology investments. However, great care is required. Some space telescope cost models, such as those based only on mass, lack sufficient detail to support such analysis and may lead to inaccurate conclusions. Similarly, using ground based telescope models which include the dome cost will also lead to inaccurate conclusions. This paper reviews current and historical models. Then, based on data from 22 different NASA space telescopes, this paper tests those models and presents preliminary analysis of single and multi-variable space telescope cost models
Paracetamol reduces influenza-induced immunopathology in a mouse model of infection without compromising virus clearance or the generation of protective immunity
Background: Seasonal influenza A infection affects a significant cohort of the global population annually, resulting in considerable morbidity and mortality. Therapeutic strategies are of limited efficacy, and during a pandemic outbreak would only be available to a minority of the global population. Over-the-counter medicines are routinely taken by individuals suffering from influenza, but few studies have been conducted to determine their effectiveness in reducing pulmonary immunopathology or the influence they exert upon the generation of protective immunity. Methods: A mouse model of influenza infection was utilised to assess the efficacy of paracetamol (acetaminophen) in reducing influenza-induced pathology and to examine whether paracetamol affects generation of protective immunity. Results: Administration (intraperitoneal) of paracetamol significantly decreased the infiltration of inflammatory cells into the airway spaces, reduced pulmonary immunopathology associated with acute infection and improved the overall lung function of mice, without adversely affecting the induction of virus-specific adaptive responses. Mice treated with paracetamol exhibited an ability to resist a second infection with heterologous virus comparable with that of untreated mice. Conclusions: Our results demonstrate that paracetamol dramatically reduces the morbidity associated with influenza but does not compromise the development of adaptive immune responses. Overall, these data support the utility of paracetamol for reducing the clinical symptoms associated with influenza virus infection
A distinct chemokine axis does not account for enrichment of Foxp3+ CD4+T cells in carcinogen-induced fibrosarcomas
The frequency of CD4+ Foxp3+ regulatory T (Treg) cells is often significantly
increased in the blood of tumour-bearing mice and people with
cancer. Moreover, Treg cell frequencies are often higher in tumours compared
with blood and lymphoid organs. We wished to determine whether
certain chemokines expressed within the tumour mass selectively recruit
Treg cells, thereby contributing to their enrichment within the tumourinfiltrating
lymphocyte pool. To achieve this goal, the chemokine profile
of carcinogen-induced fibrosarcomas was determined, and the chemokine
receptor expression profiles of both CD4+ Foxp3
�
and CD4+ Foxp3+ T
cells were compared. These analyses revealed that the tumours are characterized
by expression of inflammatory chemokines (CCL2, CCL5, CCL7,
CCL8, CCL12, CXCL9, CXCL10 and CX3CL1), reflected by an enrichment
of activated Foxp3
�
and Foxp3+ T cells expressing T helper type 1-
associated chemokine receptors. Notably, we found that CXCR3+ T cells
were significantly enriched in the tumours although curiously we found
no evidence that CXCR3 was required for their recruitment. Instead,
CXCR3 marks a population of activated Foxp3
�
and Foxp3+ T cells,
which use multiple and overlapping ligand receptor pairs to guide their
migration to tumours. Collectively, these data indicate that enrichment of
Foxp3+ cells in tumours characterized by expression of inflammatory
chemokines, does not occur via a distinct chemokine axis, thus selective
chemokine blockade is unlikely to represent a meaningful therapeutic
strategy for preventing Treg cell accumulation in tumours
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Real World Performance of the 21st Century Cures Act Population Level Application Programming Interface
OBJECTIVE: To evaluate the real-world performance in delivering patient data on populations, of the SMART/HL7 Bulk FHIR Access API, required in Electronic Health Records (EHRs) under the 21st Century Cures Act Rule. MATERIALS AND METHODS: We used an open-source Bulk FHIR Testing Suite at five healthcare sites from April to September 2023, including four hospitals using EHRs certified for interoperability, and one Health Information Exchange (HIE) using a custom, standards-compliant API build. We measured export speeds, data sizes, and completeness across six types of FHIR resources. RESULTS: Among the certified platforms, Oracle Cerner led in speed, managing 5-16 million resources at over 8,000 resources/min. Three Epic sites exported a FHIR data subset, achieving 1-12 million resources at 1,555-2,500 resources/min. Notably, the HIE's custom API outperformed, generating over 141 million resources at 12,000 resources/min. DISCUSSION: The HIE's custom API showcased superior performance, endorsing the effectiveness of SMART/HL7 Bulk FHIR in enabling large-scale data exchange while underlining the need for optimization in existing EHR platforms. Agility and scalability are essential for diverse health, research, and public health use cases. CONCLUSION: To fully realize the interoperability goals of the 21st Century Cures Act, addressing the performance limitations of Bulk FHIR API is critical. It would be beneficial to include performance metrics in both certification and reporting processes
The histone deacetylase inhibitor, romidepsin, as a potential treatment for pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF) is a progressive disease that usually affects elderly people. It has a poor prognosis and there are limited therapies. Since epigenetic alterations are associated with IPF, histone deacetylase (HDAC) inhibitors offer a novel therapeutic strategy to address the unmet medical need. This study investigated the potential of romidepsin, an FDA-approved HDAC inhibitor, as an anti-fibrotic treatment and evaluated biomarkers of target engagement that may have utility in future clinical trials. The anti-fibrotic effects of romidepsin were evaluated both in vitro and in vivo together with any harmful effect on alveolar type II cells (ATII). Bronchoalveolar lavage fluid (BALF) from IPF or control donors was analyzed for the presence of lysyl oxidase (LOX). In parallel with an increase in histone acetylation, romidepsin potently inhibited fibroblast proliferation, myofibroblast differentiation and LOX expression. ATII cell numbers and their lamellar bodies were unaffected. In vivo, romidepsin inhibited bleomycin-induced pulmonary fibrosis in association with suppression of LOX expression. LOX was significantly elevated in BALF of IPF patients compared to controls. These data show the anti-fibrotic effects of romidepsin, supporting its potential use as novel treatment for IPF with LOX as a companion biomarker for evaluation of early on-target effects
RRAF Report
Smith-Yoshimura K, Altman M, Conlon M, et al. Registering Researchers in Authority Files. online: OCLC Research; 2014.Registering researchers in some type of authority file or identifier system has become more compelling as both institutions and researchers recognize the need to compile their scholarly output. The report presents functional requirements and recommendations for six stakeholders: researchers, funders, university administrators, librarians, identity management systems, and aggregators (including publishers). It also provides an overview of the researcher identifier landscape, changes in the field, emerging trends, and opportunities
Interleukin-6 limits influenza-induced inflammation and protects against fatal lung pathology
Balancing the generation of immune responses capable of controlling virus replication with those causing immunopathology is critical for the survival of the host and resolution of influenza-induced inflammation. Based on the capacity of interleukin-6 (IL-6) to govern both optimal T-cell responses and inflammatory resolution, we hypothesised that IL-6 plays an important role in maintaining this balance. Comparison of innate and adaptive immune responses in influenza-infected wild-type control and IL-6-deficient mice revealed striking differences in virus clearance, lung immunopathology and generation of heterosubtypic immunity. Mice lacking IL-6 displayed a profound defect in their ability to mount an anti-viral T-cell response. Failure to adequately control virus was further associated with an enhanced infiltration of inflammatory monocytes into the lung and an elevated production of the pro-inflammatory cytokines, IFN-α and TNF-α. These events were associated with severe lung damage, characterised by profound vascular leakage and death. Our data highlight an essential role for IL-6 in orchestrating anti-viral immunity through an ability to limit inflammation, promote protective adaptive immune responses and prevent fatal immunopathology
Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial
Background
Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy
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