Using facial feature extraction to enhance the creation of 3D human models

The creation of personalised 3D characters has evolved to provide a high degree of realism in both appearance and animation. Further to the creation of generic characters the capabilities exist to create a personalised character from images of an individual. This provides the possibility of immersing an individual into a virtual world. Feature detection, particularly on the face, can be used to greatly enhance the realism of the model. To address this innovative contour based templates are used to extract an individual from four orthogonal views providing localisation of the face. Then adaptive facial feature extraction from multiple views is used to enhance the realism of the model

Efficacy and safety of mavrilimumab in giant cell arteritis:a phase 2, randomised, double-blind, placebo-controlled trial

OBJECTIVES: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is implicated in pathogenesis of giant cell arteritis. We evaluated the efficacy of the GM-CSF receptor antagonist mavrilimumab in maintaining disease remission. METHODS: This phase 2, double-blind, placebo-controlled trial enrolled patients with biopsy-confirmed or imaging-confirmed giant cell arteritis in 50 centres (North America, Europe, Australia). Active disease within 6 weeks of baseline was required for inclusion. Patients in glucocorticoid-induced remission were randomly assigned (3:2 ratio) to mavrilimumab 150 mg or placebo injected subcutaneously every 2 weeks. Both groups received a 26-week prednisone taper. The primary outcome was time to adjudicated flare by week 26. A prespecified secondary efficacy outcome was sustained remission at week 26 by Kaplan-Meier estimation. Safety was also assessed. RESULTS: Of 42 mavrilimumab recipients, flare occurred in 19% (n=8). Of 28 placebo recipients, flare occurred in 46% (n=13). Median time to flare (primary outcome) was 25.1 weeks in the placebo group, but the median was not reached in the mavrilimumab group (HR 0.38; 95% CI 0.15 to 0.92; p=0.026). Sustained remission at week 26 was 83% for mavrilimumab and 50% for placebo recipients (p=0.0038). Adverse events occurred in 78.6% (n=33) of mavrilimumab and 89.3% (n=25) of placebo recipients. No deaths or vision loss occurred in either group. CONCLUSIONS: Mavrilimumab plus 26 weeks of prednisone was superior to placebo plus 26 weeks of prednisone for time to flare by week 26 and sustained remission in patients with giant cell arteritis. Longer treatment is needed to determine response durability and quantify the glucocorticoid-sparing potential of mavrilimumab. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number: NCT03827018, Europe (EUdraCT number: 2018-001003-36), and Australia (CT-2018-CTN-01 865-1)

Proneoplastic effects of PGE2 mediated by EP4 receptor in colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Prostaglandin E₂(PGE₂) is the major product of Cyclooxygenase-2 (COX-2) in colorectal cancer (CRC). We aimed to assess PGE₂cell surface receptors (EP 1–4) to examine the mechanisms by which PGE₂regulates tumour progression.</p> <p>Methods</p> <p>Gene expression studies were performed by quantitative RT-PCR. Cell cycle was analysed by flow cytometry with cell proliferation quantified by BrdU incorporation measured by enzyme immunoassay. Immunohistochemistry was employed for expression studies on formalin fixed paraffin embedded tumour tissue.</p> <p>Results</p> <p>EP4 was the most abundant subtype of PGE₂receptor in HT-29 and HCA7 cells (which show COX-2 dependent PGE₂generation) and was consistently the most abundant transcript in human colorectal tumours (n = 8) by qRT-PCR (ANOVA, p = 0.01). G0/G1 cell cycle arrest was observed in HT-29 cells treated with SC-236 5 μM (selective COX-2 inhibitor) for 24 hours (p = 0.02), an effect abrogated by co-incubation with PGE₂(1 μM). G0/G1 arrest was also seen with a specific EP4 receptor antagonist (EP4A, L-161982) (p = 0.01). Treatment of HT-29 cells with either SC-236 or EP4A caused reduction in intracellular cAMP (ANOVA, p = 0.01). Early induction in p21^WAF1/CIP1expression (by qRT-PCR) was seen with EP4A treatment (mean fold increase 4.4, p = 0.04) while other genes remained unchanged. Similar induction in p21^WAF1/CIP1was also seen with PD153025 (1 μM), an EGFR tyrosine kinase inhibitor, suggesting EGFR transactivation by EP4 as a potential mechanism. Additive inhibition of HCA7 proliferation was observed with the combination of SC-236 and neutralising antibody to amphiregulin (AR), a soluble EGFR ligand. Concordance in COX-2 and AR localisation in human colorectal tumours was noted.</p> <p>Conclusion</p> <p>COX-2 regulates cell cycle transition via EP4 receptor and altered p21^WAF1/CIP1expression. EGFR pathways appear important. Specific targeting of the EP4 receptor or downstream targets may offer a safer alternative to COX-2 inhibition in the chemoprevention of CRC.</p

A genome-wide association study identifies risk alleles in plasminogen and P4HA2 associated with giant cell arteritis

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analysed in 2,134 cases and 9,125 unaffected controls from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, P = 1.94E-54, per-allele OR = 1.79; and rs9275592, P = 1.14E-40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, P = 1.23E-10, OR = 1.28; and rs128738, P = 4.60E-09, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis

Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status

Abstract: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA

Practice Theory and Management Research

With over 100 entries on key concepts and theorists, the Dictionary of Qualitative Management Research provides full coverage of the field, explaining fundamental concepts and introducing new and unfamiliar terms. This book provides: - Definitions - Examples in the field of management studies - Criticisms and possible future directions Engagingly written by specialists in each area, this dictionary will be the definitive and essential companion to established textbooks and teaching materials in qualitative management research

Organising Organising: the Practice inside the Process

This paper explores the contradictory pressures for standardisation and customisation in reorganisation processes. Taking a ‘practice lens’ (Orlikowski, 2000), it examines eight on-going reorganisations, from both private and non-private sectors, using photography, observation and extensive interviews. This practice lens goes both outside and inside the processes of reorganising. Outside these processes, it highlights the pervasive influence of standard, even banalised practices, from those embedded in the technologies of Microsoft to the frameworks of McKinsey &amp; Co. Inside these processes, it emphasises the detailed improvisation around these standard practices, with customising the norm. The paper concludes by arguing for the effectiveness of the practice lens in negotiating the contradictory pressures between standardisation and customisation, and by offering provisional implications for the teaching of organisation design in business schools

Delusion, Deception,and Corruption in Major Infrastructure Projects: Causes, Consequences, Cures.

The successful delivery of major infrastructure projects is increasingly vital to the global economy, with an estimated $22 trillion in projected investments to be spent in emerging economies alone (The Economist, June 7, 2008). Projected benefits include employment, the purchase of domestic inputs, improvements in productivity and competitiveness as a consequence of lower producer costs, provision of higher quality services to consumers, and environmental benefits arising from the use of new environmentally sound technologies (Helm, 2008). Yet, the track record for delivery of major infrastructure projects is poor, typically characterized by enormous cost overruns and benefits shortfalls (Merrow et al., 1988; Miller and Lessard, 2000; Flyvbjerg et al., 2003). Further, infrastructure is the third member of an ‘unholy trinity’ of high-risk sectors alongside arms and energy, suffering from substantial exposure to corruption (Transparency International, 2010). Global economic and development ambitions, therefore, rest on shaky foundations

Practices of strategising/organising: Broadening strategy work and skills

This article examines three practices of strategising/organising – strategy workshops, the project management of strategic and organisational initiatives, and the creation of symbolic artefacts to communicate strategic change. These are seen through a practice theory lens that emphasises practical activity and the tight linkage between strategising and organising. The article argues that, in a world of accelerating change, approaching strategy and organisation as interlinked and practical activities is more effective than traditional static and detached approaches that, privilege analysis. As change drives repeated strategising/organising, it is mastery of the tools and procedures that matters, at least as much as the perfection of any transitory design. Drawing on a qualitative study of ten strategic reorganisations, the article analyses particular vignettes of strategy workshops, strategy projects and strategy artefacts in action. A common theme across all three practices is the importance of hands-on, practical crafting skills in getting strategising done. The article argues for a greater recognition of these kinds of craft skills in strategy, alongside traditional analytical skills, and addresses implications for practitioners and business schools. For practitioners, there is no need to reject formal strategy making, as some critics have proposed. Rather, practitioners can renew formal strategy by injecting craft directly into the process. Business schools, as managerial trainers for the strategy process, should extend both their research and their teaching. Strategy research needs to move beyond its traditional domain of economic analysis in order to understand the whole range of effective practices in strategising/organising work, drawing on close observation of what strategists actually do. Strategy teaching needs to bring the practicalities of strategising/organising work directly into the mainstream strategy curriculum, instead of marginalizing them into adjacent sub-disciplines such as consulting skills