Development of technology maturity framework in managing manufacturing improvement for innovation providers

Readiness measurement frameworks have been used in different sectors of industry for many years. Many companies described them as essential when considering product development processes. Unfortunately, most of these frameworks cannot be directly applied in research centre environment for two reasons: too complicated, and not relevant to research centres‟ nature of work (Gove and Uzdzinski, 2013; Lind et al., 2013; Mankinsab, 2009). In addition, innovation providers have to consider global megatrends and the way they influence the community especially the manufacturing sector. For example, an increasing demand for customised nano- and macro- technologies has been observed and this trend has created a great impact on technological innovations and directions that research projects will follow in the coming years. This study focuses on manufacturing sector as this sector is mostly affected by the megatrends (Hajkowicz, 2015; Korn Ferry Hay Group, 2016; Ernest & Young, 2015). As existing industrial frameworks are not applicable at research centres, there is a need for developing new framework that would help not only with monitoring technology development processes, but also with decision-making processes. In fact, the majority of research centres in the UK often use road-mapping to evaluate and decide what would be their next actions. However, road-mapping was sometimes described as unreliable and hard to validate (Kostoff & Schaller, 2001). Anew framework would therefore be a better alternative. Preliminary studies suggested that there is a need for a new research centre-oriented framework, hence called technology maturity (Dombrowski et al., 2016; Gove & Uzdzinski, 2013). Moreover, given the importance of megatrends to the manufacturing sector, technology maturity, is found crucial when developing new technological solutions and considering so-called "valley of death", i.e. the transition from the innovation stage to the competitive manufacturing stage. Therefore, the main goal of this paper is to develop a conceptual maturity framework and support research centres to enter Industry 4.0 by overcoming some of the modern engineering issues such as "valley of death"

Three dimensions of maturity required to achieve future state, technology-enabled manufacturing supply chains

The particular challenges associated with supply chain application of emerging manufacturing technologies are increasingly recognised in industry, academia and government. The problem is often described in terms of Technology Readiness Levels (TRLs), with the particular challenge relating to the stages between proof of concept and initial adoption in the factory environment. In the UK the government has established the High Value Manufacturing Catapult, a network of manufacturing innovation centres brought together with the objective of addressing the so called ‘valley of death’ between traditional academic research and industrial needs across a broad spectrum of manufacturing process technology. This is achieved through demonstrating manufacturing technology at full scale, in factory representative environments in terms of equipment, process control and operation. This provision helps to address the key gap of full scale pre-production capability demonstration and can be seen to de-risk investment in new manufacturing technology. This paper argues that addressing this particular gap is entirely necessary but not sufficient to drive exploitation of the full potential that is available from the latest manufacturing technologies. A three dimensional maturity based framework is proposed which, in addition to considerations of technology demonstration, also allows the position of the target product application in its product lifecycle, and the readiness of the supply chain to receive the technology to be taken into account as success factors in the potential for industrialisation. Case study examples, both current and historical, are used to illustrate the need for such an approach in achieving future technology enabled supply chains. In combination this analysis introduces the basis of a more complete ‘long valley of death’ description which articulates the needs of research networks to establish a level of foundational capability ahead of specific client readiness projects in order to maximise overall pace and achieve a level of agility of delivery which is consistent with future views on digitalisation of manufacture

Antibiotic exposure within six months before systemic therapy was associated with lower cancer survival.

OBJECTIVES: The objective of the study was to quantify associations between cancer survival and antibiotic exposure before systemic anticancer therapy. STUDY DESIGN AND SETTING: This population-based cohort study compares cause-specific survival according to antibiotic exposure before non-immune checkpoint inhibitor (ICI) systemic therapy in patients diagnosed with single primary cancers in New South Wales between 2013 and 2016. Proportional hazards regression was used to control for confounding, with no antibiotic exposure in the six months before non-ICI systemic therapy serving as the comparator. RESULTS: After adjusting for tumour spread, cancer site, age, sex and comorbidity, people having antibiotic exposure within 180 days before non-ICI systemic therapy had poorer cancer survival (hazard ratios ranging from 1.21 [95% confidence interval: 1.06-1.39] to 1.58 [1.34-1.87]) for shorter periods since antibiotic exposure (P < .0001). Similarly, poorer survival trends applied for localized and metastatic cancer. Of six prevalent cancers studied, lung and breast primaries showed the strongest associations of lower survival with prior antibiotic exposure. CONCLUSION: Antibiotic exposure within 180 days before non-ICI systemic cancer treatment is associated with poorer survival. If confirmed in other studies, it provides another reason for vigilant antibiotic stewardship

The effect of prior healthcare employment on the wages of registered nurses

© 2016 The Author(s).Background: The proportion of registered nurses (RNs) with employment in health-related positions before their initial RN education has increased in the past two decades. Previous research found that prior health-related employment i

TLR7 activation at epithelial barriers promotes emergency myelopoiesis and lung antiviral immunity

Monocytes are heterogeneous innate effector leukocytes generated in the bone marrow and released into circulation in a CCR2-dependent manner. During infection or inflammation, myelopoiesis is modulated to rapidly meet the demand for more effector cells. Danger signals from peripheral tissues can influence this process. Herein we demonstrate that repetitive TLR7 stimulation via the epithelial barriers drove a potent emergency bone marrow monocyte response in mice. This process was unique to TLR7 activation and occurred independently of the canonical CCR2 and CX3CR1 axes or prototypical cytokines. The monocytes egressing the bone marrow had an immature Ly6C-high profile and differentiated into vascular Ly6C-low monocytes and tissue macrophages in multiple organs. They displayed a blunted cytokine response to further TLR7 stimulation and reduced lung viral load after RSV and influenza virus infection. These data provide insights into the emergency myelopoiesis likely to occur in response to the encounter of single-stranded RNA viruses at barrier sites

Genetic Economy in Picornaviruses: Foot-and-Mouth Disease Virus Replication Exploits Alternative Precursor Cleavage Pathways

The RNA genomes of picornaviruses are translated into single polyproteins which are subsequently cleaved into structural and non-structural protein products. For genetic economy, proteins and processing intermediates have evolved to perform distinct functions. The picornavirus precursor protein, P3, is cleaved to produce membrane-associated 3A, primer peptide 3B, protease 3Cpro and polymerase 3Dpol. Uniquely, foot-and-mouth disease virus (FMDV) encodes three similar copies of 3B (3B1-3), thus providing a convenient natural system to explore the role(s) of 3B in the processing cascade. Using a replicon system, we confirmed by genetic deletion or functional inactivation that each copy of 3B appears to function independently to prime FMDV RNA replication. However, we also show that deletion of 3B3 prevents replication and that this could be reversed by introducing mutations at the C-terminus of 3B2 that restored the natural sequence at the 3B3-3C cleavage site. In vitro translation studies showed that precursors with 3B3 deleted were rapidly cleaved to produce 3CD but that no polymerase, 3Dpol, was detected. Complementation assays, using distinguishable replicons bearing different inactivating mutations, showed that replicons with mutations within 3Dpol could be recovered by 3Dpol derived from “helper” replicons (incorporating inactivation mutations in all three copies of 3B). However, complementation was not observed when the natural 3B-3C cleavage site was altered in the “helper” replicon, again suggesting that a processing abnormality at this position prevented the production of 3Dpol. When mutations affecting polyprotein processing were introduced into an infectious clone, viable viruses were recovered but these had acquired compensatory mutations in the 3B-3C cleavage site. These mutations were shown to restore the wild-type processing characteristics when analysed in an in vitro processing assay. Overall, this study demonstrates a dual functional role of the small primer peptide 3B3, further highlighting how picornaviruses increase genetic economy

Submillimeter Studies of Prestellar Cores and Protostars: Probing the Initial Conditions for Protostellar Collapse

Improving our understanding of the initial conditions and earliest stages of protostellar collapse is crucial to gain insight into the origin of stellar masses, multiple systems, and protoplanetary disks. Observationally, there are two complementary approaches to this problem: (1) studying the structure and kinematics of prestellar cores observed prior to protostar formation, and (2) studying the structure of young (e.g. Class 0) accreting protostars observed soon after point mass formation. We discuss recent advances made in this area thanks to (sub)millimeter mapping observations with large single-dish telescopes and interferometers. In particular, we argue that the beginning of protostellar collapse is much more violent in cluster-forming clouds than in regions of distributed star formation. Major breakthroughs are expected in this field from future large submillimeter instruments such as Herschel and ALMA.Comment: 12 pages, 9 figures, to appear in the proceedings of the conference "Chemistry as a Diagnostic of Star Formation" (C.L. Curry & M. Fich eds.

Transpiration from subarctic deciduous woodlands: environmental controls and contribution to ecosystem evapotranspiration

Potential land‐climate feedbacks in subarctic regions, where rapid warming is driving forest expansion into the tundra, may be mediated by differences in transpiration of different plant functional types. Here we assess the environmental controls of overstorey transpiration and its relevance for ecosystem evapotranspiration in subarctic deciduous woodlands. We measured overstorey transpiration of mountain birch canopies and ecosystem evapotranspiration in two locations in northern Fennoscandia, having dense (Abisko) and sparse (Kevo) overstories. For Kevo, we also upscale chamber‐measured understorey evapotranspiration from shrubs and lichen using a detailed land cover map. Sub‐daily evaporative fluxes were not affected by soil moisture, and showed similar controls by vapour pressure deficit and radiation across sites. At the daily timescale, increases in evaporative demand led to proportionally higher contributions of overstorey transpiration to ecosystem evapotranspiration. For the entire growing season, the overstorey transpired 33% of ecosystem evapotranspiration in Abisko and only 16% in Kevo. At this latter site, the understorey had a higher leaf area index and contributed more to ecosystem evapotranspiration compared to the overstorey birch canopy. In Abisko, growing season evapotranspiration was 27% higher than precipitation, consistent with a gradual soil moisture depletion over the summer. Our results show that overstorey canopy transpiration in subarctic deciduous woodlands is not the dominant evaporative flux. However, given the observed environmental sensitivity of evapotranspiration components, the role of deciduous trees in driving ecosystem evapotranspiration may increase with the predicted increases in tree cover and evaporative demand across subarctic regions

Pathological Investigation of Congenital Bicuspid Aortic Valve Stenosis, Compared with Atherosclerotic Tricuspid Aortic Valve Stenosis and Congenital Bicuspid Aortic Valve Regurgitation

Congenital bicuspid aortic valve (CBAV) is the main cause of aortic stenosis (AS) in young adults. However, the histopathological features of AS in patients with CBAV have not been fully investigated.We examined specimens of aortic valve leaflets obtained from patients who had undergone aortic valve re/placement at our institution for severe AS with CBAV (n = 24, CBAV-AS group), severe AS with tricuspid aortic valve (n = 24, TAV-AS group), and severe aortic regurgitation (AR) with CBAV (n = 24, CBAV-AR group). We compared the histopathological features among the three groups. Pathological features were classified using semi-quantitative methods (graded on a scale 0 to 3) by experienced pathologists without knowledge of the patients' backgrounds. The severity of inflammation, neovascularization, and calcium and cholesterol deposition did not differ between the CBAV-AS and TAV-AS groups, and these four parameters were less marked in the CBAV-AR group than in the CBAV-AS (all p<0.01). Meanwhile, the grade of valvular fibrosis was greater in the CBAV-AS group, compared with the TAV-AS and CBAV-AR groups (both p<0.01). In AS patients, thickness of fibrotic lesions was greater on the aortic side than on the ventricular side (both p<0.01). Meanwhile, thickness of fibrotic lesions was comparable between the aortic and ventricular sides in CBAV-AR patients (p = 0.35).Valvular fibrosis, especially on the aortic side, was greater in patients with CBAV-AS than in those without, suggesting a difference in the pathogenesis of AS between CBAV and TAV