A sustainable approach to financial turnaround of a mature business within the UK steel industry

PhD ThesisThe UK steel industry is an example of a mature industry that has failed to cope with the harsh realities of changing market dynamics. Since nationalisation its response has been predicated upon cost and asset retrenchment. However, this alone has failed to address decline in sales and poor financial returns. Consequently, the UKs market share within home and global markets has been eroded and will continue as such unless it can address its ability to differentiate the product it offers. This thesis has considered the cause(s) of organisational failure and the development of an appropriate turnaround strategy. As an Action Researcher this has involved understanding how change introduced in the work place was accepted within the social context of that environment. Fieldwork undertaken within Corus Tubes Energy (CTE), considered by the Researcher to be representative of the UK steel industry, included both primary and secondary methods of data capture and analysis. For example, interviews, observation, narrative and content analysis, followed by periods of reflection as theories were constructed and tested. Investigative studies concluded that for CTE to compete effectively it had to differentiate itself as a high-tech, low-cost competitor by addressing internal issues and improving productivity by 52%. The turnaround strategy developed by the Researcher was premised on a mutually supportive operational and HRM strategy. Lean Manufacturing (LM) was adopted as a mechanism to reform workshop practices, address operational efficiency, reduce conversion cost, extend capability and thereby address competitive position. Whilst simultaneously, outdated HRM practices were reconstituted to support the introduction and the ability to sustain a radical transformation in operational and strategic practices. The ‘adopt and adapt’ approach employed has achieved this and resulted in a sustained turnaround moving a loss-making trajectory to profit-making. The turnaround has demonstrated the viability of the business and safe-guarded jobs. The unique contribution to theory has been the development of the Sustainability Framework and the use of LM as a concept to be used to facilitate turnaround. Supportive contributions include: the extension the NEPA model through the development of a process that supports strategic change at management level within the UK steel industry; and a closed loop methodology that engaged shop floor operators in continuous improvement

A survey of 3D audio through the browser: practitioner perspectives

This paper examines the current eco-system of tools for implementing dynamic 3D audio through the browser, from the perspective of spatial sound practitioners. It presents a survey of some existing tools to assess usefulness, and ease of use. This takes the forms of case studies, interviews with other practitioners, and initial testing comparisons between the authors. The survey classifies and summarizes their relative advantages, disadvantages and potential use cases. It charts the specialist knowledge needed to employ them or enable others to. The recent and necessary move to online exhibition of works, has seen many creative practitioners grapple with a disparate eco-system of software. Such technologies are diverse in their both their motivations and applications. From formats which overcome the limits of WebGL’s lack of support for Ambisonics, to the creative deployment of Web Audio API (WAA), to third- party tools based on WAA, the field can seem prohibitively daunting for practitioners. The current range of possible acoustic results may be too unclear to justify the learning curve. Through this evaluation of the current available tools, we hope to demystify and make accessible these novel technologies to composers, musicians, artists and other learners, who might otherwise be dissuaded from engaging with this rich territory. This paper is based on a special session at Soundstack 2021

Neonatal head and torso vibration exposure during inter-hospital transfer

Inter-hospital transport of premature infants is increasingly common, given the centralisation of neonatal intensive care. However, it is known to be associated with anomalously increased morbidity, most notably brain injury, and with increased mortality from multifactorial causes. Surprisingly, there have been relatively few previous studies investigating the levels of mechanical shock and vibration hazard present during this vehicular transport pathway. Using a custom inertial datalogger, and analysis software, we quantify vibration and linear head acceleration. Mounting multiple inertial sensing units on the forehead and torso of neonatal patients and a preterm manikin, and on the chassis of transport incubators over the duration of inter-site transfers, we find that the resonant frequency of the mattress and harness system currently used to secure neonates inside incubators is ~9Hz. This couples to vehicle chassis vibration, increasing vibration exposure to the neonate. The vibration exposure per journey (A(8) using the ISO 2631 standard) was at least 20% of the action point value of current European Union regulations over all 12 neonatal transports studied, reaching 70% in two cases. Direct injury risk from linear head acceleration (HIC15) was negligible. Although the overall hazard was similar, vibration isolation differed substantially between sponge and air mattresses, with a manikin. Using a Global Positioning System datalogger alongside inertial sensors, vibration increased with vehicle speed only above 60 km/h. These preliminary findings suggest there is scope to engineer better systems for transferring sick infants, thus potentially improving their outcomes

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Cytokines and inflammatory mediators: 25. Certolizumab Pegol has a Different Profile from the other Anti-TNFS, Including Golimumab, in a Variety of in Vitro Assays

Background: Activities of the anti-TNFs, certolizumab pegol (CZP), etanercept (ETA), infliximab (IFX) and adalimumab (ADA), have been compared in a range of in vitro assays. CZP is the only licensed PEGylated Fab' anti-TNF; ETA is a fusion protein with an IgG1 Fc, and IFX and ADA are both antibodies with an IgG1 Fc. Golimumab (GLM) is a monoclonal IgG1 TNF inhibitor recently approved for a number of indications; it is thus of interest to assess the in vitro activity of GLM. In vitro assays previously used were neutralisation of TNF in the L929 bioassay, inhibition of LPS-driven cytokine production by monocytes, induction of apoptosis in activated lymphocytes and monocytes, and induction of neutrophil necrosis. Methods: Neutralisation of human TNF was assessed in the L929 bioassay using a range of concentrations of the anti-TNFs and a fixed concentration of TNF (100 pg/mL). Activity of the anti-TNFs at inhibiting LPS-driven IL-1β secretion by monocytes was assessed by incubating peripheral blood monocytes with various concentrations of the anti-TNF for 1 hour (hr) and then washing the cells. LPS was added for 4 hrs, the supernatants collected and the IL-1β level measured by ELISA. To assess induction of apoptosis, peripheral blood lymphocytes were activated for 2 days with 2 μg/mL CD3/CD28 and monocytes with 300 U/mL IL-4 and GMCSF for 3 days. The effect of the anti-TNFs on apoptosis was assessed by Annexin V staining using flow cytometry 24 hrs later. The effect of the anti-TNFs on neutrophil necrosis was determined by measuring myeloperoxidase release after 12 hrs. An isotype-matched control was used in all assays except the L929 bioassay. Results: IC90 neutralisation activity of the anti-TNFs in the L929 bioassay was 0.3 ng/mL for ETA, 4 ng/mL for GLM, 15 ng/mL for ADA, and 20 ng/mL for IFX, compared with 2.5 ng/mL for CZP. CZP was the most potent inhibitor of LPS-driven IL-1β secretion (IC50 ∼0.1 ng/mL), followed by GLM (20 ng/mL) and IFX (50 ng/mL). GLM, ADA, IFX and ETA induced apoptosis of monocytes and lymphocytes to a similar degree reaching a level of 23% and ∼40% at 100 μg/mL, respectively. CZP caused no increase in apoptosis above the levels seen with the isotype-matched control. In the neutrophil necrosis assay, ADA,IFX and GLM caused ∼70% necrosis at 100 μg/mL, and ETA 48%. CZP did not increase the level of necrosis above the level of the control. Conclusions: Bioactivity of the IgG1 molecules GLM, IFX and ADA in neutralising human TNF was inferior to that of CZP and ETA. CZP, the only PEGylated anti-TNF, had a different profile to the other anti-TNFs as it was the most potent at inhibiting LPS-driven IL-1β production by monocytes, did not induce apoptosis of activated monocytes and lymphocytes, and did not cause neutrophil necrosis. The clinical relevance of these in vitro effects is unknown. Nevertheless, these assays show interesting in vitro differences between the anti-TNFs. Disclosure statement: G.F. and A.N. are employees of UC

Adjuvant nivolumab for stage III/IV melanoma: evaluation of safety outcomes and association with recurrence-free survival.

Several therapeutic options are now available in the adjuvant melanoma setting, mandating an understanding of their benefit‒risk profiles in order to make informed treatment decisions. Herein we characterize adjuvant nivolumab select (immune-related) treatment-related adverse events (TRAEs) and evaluate possible associations between safety and recurrence-free survival (RFS) in the phase III CheckMate 238 trial. Patients with resected stage IIIB-C or IV melanoma received nivolumab 3 mg/kg every 2 weeks (n=452) or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks (n=453) for up to 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. First-occurrence and all-occurrence select TRAEs were analyzed within discrete time intervals: from 0 to 3 months of treatment, from >3-12 months of treatment, and from the last dose (regardless of early or per-protocol treatment discontinuation) to 100 days after the last dose. Possible associations between select TRAEs and RFS were investigated post randomization in 3-month landmark analyses and in Cox model analyses (including a time-varying covariate of select TRAE), within and between treatment groups. From the first nivolumab dose to 100 days after the last dose, first-occurrence select TRAEs were reported in 67.7% (306/452) of patients. First-occurrence select TRAEs were reported most frequently from 0 to 3 months (48.0%), during which the most common were pruritus (15.5%) and diarrhea (15.3%). Most select TRAEs resolved within 6 months. There was no clear association between the occurrence (or not) of select TRAEs and RFS by landmark analysis or by Cox model analysis within treatment arms or comparing nivolumab to the ipilimumab comparator arm. Results of this safety analysis of nivolumab in adjuvant melanoma were consistent with its established safety profile. In the discrete time intervals evaluated, most first-occurrence TRAEs occurred early during treatment and resolved. No association between RFS and select TRAEs was evident. NCT02388906

Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals

Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors

Evolutionary diversification of new caledonian Araucaria

New Caledonia is a global biodiversity hotspot. Hypotheses for its biotic richness suggest either that the island is a ‘museum’ for an old Gondwana biota or alternatively it has developed following relatively recent long distance dispersal and in situ radiation. The conifer genus Araucaria (Araucariaceae) comprises 19 species globally with 13 endemic to this island. With a typically Gondwanan distribution, Araucaria is particularly well suited to testing alternative biogeographic hypotheses concerning the origins of New Caledonian biota. We derived phylogenetic estimates using 11 plastid and rDNA ITS2 sequence data for a complete sampling of Araucaria (including multiple accessions of each of the 13 New Caledonian Araucaria species). In addition, we developed a dataset comprising 4 plastid regions for a wider taxon sample to facilitate fossil based molecular dating. Following statistical analyses to identify a credible and internally consistent set of fossil constraints, divergence times estimated using a Bayesian relaxed clock approach were contrasted with geological scenarios to explore the biogeographic history of Araucaria. The phylogenetic data resolve relationships within Araucariaceae and among the main lineages in Araucaria, but provide limited resolution within the monophyletic New Caledonian species group. Divergence time estimates suggest a Late Cretaceous-Cenozoic radiation of extant Araucaria and a Neogene radiation of the New Caledonian lineage. A molecular timescale for the evolution of Araucariaceae supports a relatively recent radiation, and suggests that earlier (pre-Cenozoic) fossil types assigned to Araucaria may have affinities elsewhere in Araucariaceae. While additional data will be required to adequately resolve relationships among the New Caledonian species, their recent origin is consistent with overwater dispersal following Eocene emersion of New Caledonia but is too old to support a single dispersal from Australia to Norfolk Island for the radiation of the Pacific Araucaria sect. Eutacta clade.Mai Lan Kranitz, Edward Biffin, Alexandra Clark, Michelle L. Hollingsworth, Markus Ruhsam, Martin F. Gardner, Philip Thomas, Robert R. Mill, Richard A. Ennos, Myriam Gaudeul, Andrew J. Lowe, Peter M. Hollingswort

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis