The inter-relationships of managers' work time and personal time

School of Managemen

Systemic inflammation predicts all-cause mortality: a Glasgow Inflammation Outcome Study

Introduction: Markers of the systemic inflammatory response, including C-reactive protein and albumin (combined to form the modified Glasgow Prognostic Score), as well as neutrophil, lymphocyte and platelet counts have been shown to be prognostic of survival in patients with cancer. The aim of the present study was to examine the prognostic relationship between these markers of the systemic inflammatory response and all-cause, cancer, cardiovascular and cerebrovascular mortality in a large incidentally sampled cohort.<p></p> Methods: Patients (n = 160 481) who had an incidental blood sample taken between 2000 and 2008 were studied for the prognostic value of C-reactive protein (>10mg/l, albumin (>35mg/l), neutrophil (>7.5×109/l) lymphocyte and platelet counts. Also, patients (n = 52 091) sampled following the introduction of high sensitivity C-reactive protein (>3mg/l) measurements were studied. A combination of these markers, to make cumulative inflammation-based scores, were investigated.<p></p> Results: In all patients (n = 160 481) C-reactive protein (>10mg/l) (HR 2.71, p<0.001), albumin (>35mg/l) (HR 3.68, p<0.001) and neutrophil counts (HR 2.18, p<0.001) were independently predictive of all-cause mortality. These associations were also observed in cancer, cardiovascular and cerebrovascular mortality before and after the introduction of high sensitivity C-reactive protein measurements (>3mg/l) (n = 52 091). A combination of high sensitivity C-reactive protein (>3mg/l), albumin and neutrophil count predicted all-cause (HR 7.37, p<0.001, AUC 0.723), cancer (HR 9.32, p<0.001, AUC 0.731), cardiovascular (HR 4.03, p<0.001, AUC 0.650) and cerebrovascular (HR 3.10, p<0.001, AUC 0.623) mortality. Conclusion The results of the present study showed that an inflammation-based prognostic score, combining high sensitivity C-reactive protein, albumin and neutrophil count is prognostic of all-cause mortality

Purification and Characterization of OTF-l, A Transcription Factor Regulating Cell Cycle Expression of a Human Histone H2b Gene: Demonstration of its Functional Identity with NF-III, a Factor Required for Efficient Initiation of Adenovirus DNA Replication

An octamer-binding transcription factor, OTF-l, which stimulates transcription of a human histone H2b gene, has been purified from HeLa nuclear extracts. This purification was achieved through the use of DNA affinity chromatography, and the factor was unambiguously identified by renaturation of activity following SDS-polyacrylamide gel electrophoresis. The purified factor retained the ability to efficiently stimulate H2b transcription in a reconstituted in vitro system. This effect was dependent on an intact octamer element and was observed in the absence of other H2b promoter elements (except the TATA motif). This activity is absent from nuclear extracts prepared from cells synchronized in G2. However, the apparent mass and binding activity of the factor are unchanged in Sand G2. Because this factor can stimulate transcription in a G2 extract, we suggest that the modulation of activity is due to either in vivo constraints on binding or covalent (or other) modification(s). We have demonstrated that this factor is identical, by a number of criteria, to NF-llI. Therefore, OTF-l is able to stimulate the initiation of replication of adenovirus DNA. This effect was shown to be dependent on the presence of an intact NF-llI binding site in the adenovirus origin of replication. Finally, preliminary data suggesting that we have isolated a cDNA clone for this factor are presented and discussed

To Trust or Not to Trust? Developing Trusted Digital Spaces through Timely Reliable and Personalized Provenance

Organizations are increasingly dependent on data stored and processed by distributed, heterogeneous services to make critical, high-value decisions. However, these service-oriented computing environments are dynamic in nature and are becoming ever more complex systems of systems. In such evolving and dynamic eco-system infrastructures, knowing how data was derived is of significant importance in determining its validity and reliability. To address this, a number of advocates and theorists postulate that provenance is critical to building trust in data and the services that generated it as it provides evidence for data consumers to judge the integrity of the results. This paper presents a summary of the STRAPP (trusted digital Spaces through Timely Reliable And Personalised Provenance) project, which is designing and engineering mechanisms to achieve a holistic solution to a number of real-world service-based decision-support systems

Minimum Information about a Neuroscience Investigation (MINI) Electrophysiology

This module represents the formalized opinion of the authors and the CARMEN consortium, which identifies the minimum information required to report the use of electrophysiology in a neuroscience study, for submission to the CARMEN system (www.carmen.org.uk).
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Implementing telephone triage in general practice: a process evaluation of a cluster randomised controlled trial

Background: Telephone triage represents one strategy to manage demand for face-to-face GP appointments in primary care. However, limited evidence exists of the challenges GP practices face in implementing telephone triage. We conducted a qualitative process evaluation alongside a UK-based cluster randomised trial (ESTEEM) which compared the impact of GP-led and nurse-led telephone triage with usual care on primary care workload, cost, patient experience, and safety for patients requesting a same-day GP consultation. The aim of the process study was to provide insights into the observed effects of the ESTEEM trial from the perspectives of staff and patients, and to specify the circumstances under which triage is likely to be successfully implemented. Here we report perspectives of staff. Methods: The intervention comprised implementation of either GP-led or nurse-led telephone triage for a period of 2-3 months. A qualitative evaluation was conducted using staff interviews recruited from eight general practices (4 GP triage, 4 Nurse triage) in the UK, implementing triage as part of the ESTEEM trial. Qualitative interviews were undertaken with 44 staff members in GP triage and nurse triage practices (16 GPs, 8 nurses, 7 practice managers, 13 administrative staff). Results: Staff reported diverse experiences and perceptions regarding the implementation of telephone triage, its effects on workload, and on the benefits of triage. Such diversity were explained by the different ways triage was organised, the staffing models used to support triage, how the introduction of triage was communicated across practice staff, and by how staff roles were reconfigured as a result of implementing triage. Conclusion: The findings from the process evaluation offer insight into the range of ways GP practices participating in ESTEEM implemented telephone triage, and the circumstances under which telephone triage can be successfully implemented beyond the context of a clinical trial. Staff experiences and perceptions of telephone triage are shaped by the way practices communicate with staff, prepare for and sustain the changes required to implement triage effectively, as well as by existing practice culture, and staff and patient behaviour arising in response to the changes made. Trial registration: Current Controlled Trials ISRCTN20687662. Registered 28 May 2009

Erratum: Author Correction: Identification of genes required for eye development by high-throughput screening of mouse knockouts.

[This corrects the article DOI: 10.1038/s42003-018-0226-0.]

Discovery of Soft-Drug Topical Tool Modulators of Sphingosine-1-phosphate Receptor 1 (S1PR1)

In order to study the role of S1PRs in inflammatory skin disease, S1PR modulators are dosed orally and topically in animal models of disease. The topical application of S1PR modulators in these models may, however, lead to systemic drug concentrations, which can complicate interpretation of the observed effects. We set out to design soft drug S1PR modulators as topical tool compounds to overcome this limitation. A fast follower approach starting from the drug ponesimod allowed the rapid development of an active phenolic series of soft drugs. The phenols were, however, chemically unstable. Protecting the phenol as an ester removed the instability and provided a compound that is converted by enzymatic hydrolysis in the skin to the phenolic soft drug species. In simple formulations, topical dosing of these S1PR modulators to mice led to micromolar skin concentrations but no detectable blood concentrations. These topical tools will allow researchers to investigate the role of S1PR in skin, without involvement of systemic S1PR biology

Scalable continuous production of high quality HKUST-1 via conventional and microwave heating

Metal Organic Frameworks (MOFs) are materials with large surface areas and internal volumes, which result in a number of useful properties for applications such as catalysis, separations and gas storage. However, MOFs are challenging to produce at a large scale creating a barrier to becoming truly viable alternatives to current technologies. As a first step towards industrial scale manufacture, we demonstrate here the first scalable, continuous synthesis of high-quality HKUST-1 using ethanol as the solvent, resulting in a greener and potentially much more economical process (as solvent does not decompose and thus can be recycled). We also show that microwave heating can be used to produce HKUST-1 continuously, in timescales several orders of magnitude faster than by conventional heating. We demonstrate a novel approach to microwave assisted synthesis of HKUST-1, based on a recycle loop with microwave irradiation, which is scalable under both batch and continuous conditions and allows an independent control of microwave irradiation regime and the overall reaction time. The use of microwave heating for continuous production of HKUST-1 enabled STY of 400,000 kg m−3 d−1, which is higher than any production rates reported to date, even when using the preferred high yield solvent, DMF, and is 17 times more than the highest production rates reported to date for HKUST-1 in ‘ethanol-only’ systems

Effect of synthesis conditions on formation pathways of metal organic framework (MOF-5) Crystals

Metal Organic Frameworks (MOFs) represent a class of nanoporous crystalline materials with far reaching potential in gas storage, catalysis, and medical devices. We investigated the effects of synthesis process parameters on production of MOF-5 from terephthalic acid and zinc nitrate in diethylformamide. Under favorable synthesis conditions, we systematically mapped a solid formation diagram in terms of time and temperature for both stirred and unstirred conditions. The synthesis of MOF-5 has been previously reported as a straightforward reaction progressing from precursor compounds in solution directly to the final MOF-5 solid phase product. However, we show that the solid phase formation process is far more complex, invariably transferring through metastable intermediate crystalline phases before the final MOF-5 phase is reached, providing new insights into the formation pathways of MOFs. We also identify process parameters suitable for scale-up and continuous manufacturing of high purity MOF-5