Technology confidence in early stage development of medical devices

Innovation is a critical factor in ensuring commercial success within the area of medical technology. Biotechnology and Healthcare developments require huge financial and resource investment, in-depth research and clinical trials. Consequently, these developments involve a complex multidisciplinary structure, which is inherently full of risks and uncertainty. In this context, early technology assessment and 'proof of concept' is often sporadic and unstructured. Existing methodologies for managing the feasibility stage of medical device development are predominantly suited to the later phases of development and favour detail in optimisation, validation and regulatory approval. During these early phases, feasibility studies are normally conducted to establish whether technology is potentially viable. However, it is not clear how this technology viability is currently measured. This paper aims to redress this gap through the development of a technology confidence scale, as appropriate explicitly to the feasibility phase of medical device design. These guidelines were developed from analysis of three recent innovation studies within the medical device industry.

Observation of early to full covering stages of ethylene-based CVD of graphene

Scalable growth is essential for graphene-based applications. Recent development has enabled the achievement of the scalability by use of chemical vapor deposition (CVD) at 1000°C with copper as a catalyst and methane as a precursor gas. Here we report our observation of early stage of graphene growth based on an ethylene-based CVD method, capable of reducing the growth temperature to 770°C for monolayer graphene growth on copper. We track the early stages of slow growth under low ethylene flow rate and observe the graphene domain evolution by varying the temperature and growth time. Temperature-dependence of graphene domain density gives an apparent activation energy of 1.0 eV for nucleation.

A unifying resolution-independent formulation for early vision

We present a model for early vision tasks such as denoising, super-resolution, deblurring, and demosaicing. The model provides a resolution-independent representation of discrete images which admits a truly rotationally invariant prior. The model generalizes several existing approaches: variational methods, finite element methods, and discrete random fields. The primary contribution is a novel energy functional which has not previously been written down, which combines the discrete measurements from pixels with a continuous-domain world viewed through continous-domain point-spread functions. The value of the functional is that simple priors (such as total variation and generalizations) on the continous-domain world become realistic priors on the sampled images. We show that despite its apparent complexity, optimization of this model depends on just a few computational primitives, which although tedious to derive, can now be reused in many domains. We define a set of optimization algorithms which greatly overcome the apparent complexity of this model, and make possible its practical application. New experimental results include infinite-resolution upsampling, and a method for obtaining subpixel superpixels. © 2012 IEEE.

Product life trade-offs: what if products fail early?

Increasing product life allows the embodied emissions in products to be spread across a longer period but can mean that opportunities to improve use-phase efficiency are foregone. In this paper, a model that evaluates this trade-off is presented and used to estimate the optimal product life for a range of metal-intensive products. Two strategies that have potential to save emissions are explored: (1) adding extra embodied emissions to make products more sturdy, increasing product life, and (2) increasing frequency of use, causing early product failure to take advantage of improvements in use-phase efficiency. These strategies are evaluated for two specific case studies (long-life washing machines and more frequent use of vehicles through car clubs) and for a range of embodied and use-phase intensive products under different use-phase improvement rate assumptions. Particular emphasis is placed on the fact that products often fail neither at their design life nor at their optimal life. Policy recommendations are then made regarding the targeting of these strategies according to product characteristics and the timing of typical product failure relative to optimal product life.

Simulating early adoption of alternative fuel vehicles for sustainability

We quantify the conditions that might trigger wide spread adoption of alternative fuel vehicles (AFVs) to support energy policy. Empirical review shows that early adopters are heterogeneous motivated by financial benefits, environmental appeal, new technology, and vehicle reliability. A probabilistic Monte Carlo simulation model is used to assess consumer heterogeneity for early and mass market adopters. For early adopters full battery electric vehicles (BEVs) are competitive but unable to surpass diesels or hybrids due to purchase price premium and lack of charging availability. For mass adoption, simulations indicate that if the purchase price premium of a BEV closes to within 20% of an in-class internal combustion engine (ICE) vehicle, combined with a 60% increase in refuelling availability relative to the incumbent system, BEVs become competitive. But this depends on a mass market that values the fuel economy and CO2 reduction benefits associated with BEVs. We also find that the largest influence on early adoption is financial benefit rather than pro-environmental behaviour suggesting that AFVs should be marketed by appealing to economic benefits combined with pro-environmental behaviour to motivate adoption. Monte Carlo simulations combined with scenarios can give insight into diffusion dynamics for other energy demand-side technologies. © 2012 Elsevier Inc.

Stakeholder engagement in early stage product-service system development for healthcare informatics

This paper presents the findings from four case studies on stakeholder engagement in new health information and communication technology (ICT) product-service system (PSS) development. The degree of connectivity between the new health ICT PSS and its intended operating environment has emerged to be an important contextual factor that may impact the decision of stakeholder engagement in the early stage development process. Along with the proposition of a four-level framework to guide stakeholder identification for new PSS development, three stakeholder engagement propositions that are based on the degree of connectivity are developed. Analysis has shown that there can be two types of connectivity: data and process. Moreover, each connectivity type can be characterized by how much the new PSS is connected with its environment: independent if there is no linkage, linked if it interfaces with, or incorporated if it is embedded into. Furthermore, depending upon whether and to what extent the PSS has data and process connectivity with its intended operating environment, the stakeholder engagement needs in early stage development vary. The propositions presented in this paper provide important directions for future work exploring PSS characterization and stakeholder engagement decision in early stage new PSS development in the healthcare industry. © 2013 PICMET.

Using drift nets to capture early life stages and monitor spawning of the Yangtze River Chinese sturgeon (Acipenser sinensis)

P>A sampling system for capturing sturgeon eggs using a D-shaped bottom anchored drift net was used to capture early life stages (ELS) of Chinese sturgeon, Acipenser sinensis, and monitor annual spawning success at Yichang on the Yangtze River, 1996-2004, before and just after the Three Gorges Dam began operation. Captured were 96 875 ELS (early life stages: eggs, yolk-sac larvae = eleuthero embryos, and larvae); most were eggs and only 2477 were yolk-sac larvae. Most ELS were captured in the main river channel and inside the bend at the Yichang spawning reach. Yolk-sac larvae were captured for a maximum of 3 days after hatching began, indicating quick dispersal downstream. The back-calculated day of egg fertilization over the eight years indicated a maximum spawning window of 23 days (20 October-10 November). Spawning in all years was restricted temporally, occurred mostly at night and during one or two spawning periods, each lasting several days. The brief temporal spawning window may reduce egg predation by opportunistic predators by flooding the river bottom with millions of eggs. During 1996-2002, the percentage of fertilized eggs in an annual 20-egg sample was between 63.5 to 94.1%; however, in 2003 the percentage fertilized was only 23.8%. This sudden decline may be related to the altered environmental conditions at Yichang caused by operation of the Three Gorges Dam. Further studies are needed to monitor spawning and changes in egg fertilization in this threatened population.

Effects of sediment anoxia and light on turion germination and early growth of Potamogeton crispus

Potamogeton crispus is a cosmopolitan aquatic species and is widely used as a pioneer species for vegetation restoration of eutrophic lakes. However, many restoration projects applying P. crispus turions have not been successful. Earlier studies focused on effects of light and temperature on turion germination. The purpose of this study was to determine whether sediment anoxia and light interactively affected the turion germination and early growth of P. crispus. Anoxic conditions in the experiment were produced by adding sucrose to the sediment. The germination rate of the turions was 68-73% lower in the highly anoxic condition treatment than in the control. Medium light intensity (10% of natural light at the water surface) was more favorable for germination under slightly anoxic conditions than either low or high light intensity. The growth of newly-formed sprouts was also significantly inhibited by sediment anoxia. Photosynthesis and shoot biomass were reduced under sediment anoxia, whereas total chlorophyll content, root biomass, and soluble protein content were highest in the low anoxic condition treatment. Medium light improved net photosynthesis and biomass production of the sprouts. We conclude that turion germination and sprout growth can be significantly inhibited by sediment anoxia. Medium light intensity may alleviate this inhibition by anoxia, but light has little effect when sediment anoxia is severe. For the purposes of vegetation restoration, more attention should be paid to the role of sediment anoxia, and it is necessary to improve sediment and light conditions for turion germination and early growth of P. crispus in eutrophic lakes. These results will contribute to a more complete understanding of turion germination dynamics of P. crispus and will be useful for future restoration programs.

Rana grylio virus thymidine kinase gene: an early gene of iridovirus encoding for a cytoplasmic protein

The presence of thymidine kinase (TK) is a feature of many large DNA viruses. Here, a TK gene homologue was cloned and characterized from Rana grylio virus (RGV), a member of family Iridoviridae. RGV TK encodes a protein of 195 aa with a predicted molecular mass of 22.1 kDa. Homologues of the protein were present in all the currently sequenced iridoviruses, and phylogenetic analysis showed that it was much close to cellular TK type 2 (TK2), deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK). Subsequently, Western blotting revealed TK expression increased with time from 6 h post-infection in RGV-infected cells. Using drug inhibition analysis by protein synthesis inhibitor (cycloheximide) and DNA replication inhibitor (cytosine arabinofuranoside), RGV TK was classified as the early expression gene during in vitro infection. Subcellular localization by TK-GFP fusion protein expression and immunofluorescence staining showed RGV TK was an exclusively cytoplasmic protein in fish cells. Collectively, current data indicate that RGV TK was an early gene of iridovirus which encoded a cytoplasmic protein in fish cells.

Transport-determined early growth and development of jack mackerel Trachurus japonicus juveniles immigrating into Sagami Bay, Japan

Oceanographic conditions and transport processes are often critical factors that affect the early growth, survival and recruitment of marine fishes. Sagittal otoliths were analysed to determine age and early growth for 381 jack mackerel (Trachurus japonicus) juveniles from Sagami Bay on the Pacific coast of Japan. Two separate hatching periods ( December and February-March) were identified. They originated from the spawning grounds in the East China Sea. Early growth and developmental rates of December-hatching fish were lower than those for February-March-hatching fish. It is likely that these differences were determined in the Kuroshio Current during transport from the spawning grounds to Sagami Bay, and the lower December water temperatures in the bay. Origin and hatch dates of juveniles in Sagami Bay were in contrast to previous research on Fukawa Bay, where April-or-later-hatching fish from spawning grounds in the coastal waters of southern Japan constituted about half of the juvenile population. Management of these two jack mackerel stocks needs to consider these differences in hatch date composition and spawning origins, as these differences could affect early growth and subsequent mortality.

Enduring Borderlands: the Marches of Ireland and Wales in the Early Modern Period

This joint chapter explores similarities and differences between two borderlands within the early modern ‘British’ state – the marches of Ireland and Wales. In some respects, the two regions were very different, most fundamentally because the Irish march remained militarised throughout the Tudor period, while Welsh society was markedly more peaceful. However, there was also much in common. In the later middle ages both marches were frontiers between the expanding Anglo-Normans and native Celtic society. The notion that the march separated ‘civility’ from ‘savagery’ was an enduring one: despite the efforts of the Tudors to impose centralisation and uniformity throughout its territories, there remained institutions, structures of power, and mentalities which ensured that both sets of marches were still in existence by the end of the 16th century. This chapter explores the reasons for the endurance of these borderlands, and indicates how political reforms of the 16th century caused the perception – and sometimes the very location – of the marches to alter.

Characterization of an early gene encoding for dUTPase in Rana grylio virus

dUTPase (DUT) is a ubiquitous and important enzyme responsible for regulating levels of dUTP. Here, an iridovirus DUT was identified and characterized from Rana grylio virus (RGV) which is a pathogen agent in pig frog. The DUT encodes a protein of 164aa with a predicted molecular mass of 17.4 kDa, and its transcriptional initiation site was determined by 5'RACE to start from the nucleotide A at 15 nt upstream of the initiation codon ATG. Sequence comparisons and multiple alignments suggested that RGV DUT was quite similar to other identified DUTs that function as homotrimers. Phylogenetic analysis implied that DUT horizontal transfers might have occurred between the vertebrate hosts and iridoviruses. Furthermore, its temporal expression pattern during RGV infection course was characterized by RT-PCR and Western blot analysis. It begins to transcribe and translate as early as 4 h postinfection (p.i.), and remains detectable at 48 h p.i. DUT-EGFP fusion protein was observed in the cytoplasm of pEGFP-N3-Dut transfected EPC cells. Immunofluorescence also confirmed DUT cytoplasm localization in RGV-infected cells. Using drug inhibition analysis by a de novo protein synthesis inhibitor (cycloheximide) and a viral DNA replication inhibitor (cytosine arabinofuranoside), RGV DUT was classified as an early (E) viral gene during the in vitro infection. Moreover, RGV DUT overexpression was shown that there was no effect on RGV replication by viral replication kinetics assay. (c) 2006 Published by Elsevier B.V.

Early ontogeny of Ancherythroculter nigrocauda and effects of delayed first feeding on larvae

Development of embryos and larvae in Ancherythroculter nigrocauda Yih et Woo (1964) and effects of delayed first feeding on larvae were observed after artificial fertilization. The fertilized eggs were incubated at an average temperature of 26.5 degrees C (range: 25.7-27) and the larvae reared at temperatures ranging from 21.8 to 28 degrees C. First cleavage was at 50 min, epiboly began at 7 h 5 min, heartbeat reached 72 per min at 24 h 40 min and hatching occurred at 43 h 15 min after insemination. Mean total length of newly hatched larvae was 4.04 +/- 0.03 mm (n = 15). A one-chambered gas bladder was observed at 70 h 50 min, two chambers occurred at 15 days, and scales appeared approximately 30 days after hatching. Larvae began to feed exogenously at day 4 post-hatch at an average temperature of 24 degrees C. Food deprivation resulted in a progressive atrophy of skeletal muscle fibres, deterioration of the larval digestive system and cessation of organ differentiation. Larval growth under food deprivation was significantly affected by the time of first exogenous feeding. Starved larvae began to shrink, with negative growth from day 6 post-hatch. The point of no return (PNR) was reached at day 11 after hatching. Mortality of starved larvae increased sharply from day 12 after hatching.

Rearing of Procypris rabaudi during early life-history stages

The early life-history of Chinese rock carp Procypris rabaudi was investigated during a 56-day rearing period: 318 artificially propagated P. rabaudi larvae were reared throughout metamorphosis in a small-scale recirculation system (345 L water volume, 10 x 18 L rearing tanks, 150 L storage and filter compartment with bioballs, 20-30 larvae L-1) at the Institute of Hydrobiology, Wuhan, Hubei Province, China. The newly hatched larvae had an initial total length of 8.93 +/- 0.35 mm SD (n = 10) at 3 days post-hatch and reached an average total length of 33.29 mm (+/- 1.88 mm SD, n = 10) 56 days after hatching. Length increment averaged 0.45 mm day(-1), resulting in a mean growth of 24.4 mm within the 56-day period. High mortality rates of up to 92% derived from an introduced fungus infection and subsequent treatment stress with malachite green. Our results indicate that Chinese rock carp can be raised successfully from artificially fertilized eggs. We therefore assume this species to be a candidate for commercial aquaculture.