Measurement and correlation of acoustic emissions and pressure stimulated voltages in rock using an electric potential sensor

Previous laboratory-based studies have demonstrated pressure stimulated currents and electromagnetic emissions in rock and cement mortar can be used to assess damage. There is some debate whether the current and electromagnetic emission measurement technologies used thus far are viable for field application. The results presented here provide evidence that electric potential sensors are a viable new technology for field monitoring of electrical emissions. Cylindrical specimens of rock were loaded at constant stress or strain rates until failure occurred; strain gauges, piezoelectric transducers and electric potential sensors were used to monitor the strain, acoustic emissions and pressure stimulated voltages. Pressure stimulated voltages were observed in the linear elastic and inelastic deformation regions of loading, suggesting that pressure stimulated voltages are associated with microcracking and macrocracking events. Electric potential sensors are potentially a cost effective and more advanced alternative to piezo transducers and geophones for structural health monitoring of rocks

Holocene Settlement History of the Dundas Islands Archipelago, Northern British Columbia

As this article demonstrates, the Dundas Islands have been home to humans for at least eleven thousand years. This occupation was at times very extensive; this relatively small group of islands was likely home to a population of several thousand people by about two thousand years ago. While geographically on the “outer shores” of Northern Tsimshian traditional territory, these islands were in no way marginal as locations for settlement. We outline the settlement history of the archipelago by presenting the results of the Dundas Islands Archaeological Project, including the radiocarbon dating program results combined with data from three previous small-scale surveys (Archer 2000; Haggarty 1988; Inglis 1975). We discuss different types of habitation sites and chronological trends in their occupation to argue that the Dundas Islands have been near-continuously occupied for at least the entire Holocene and that this was central, not peripheral, to the broader history of human occupation in the region

''Remembering'' World War II and willingness to fight : sociocultural factors in the social representation of historical warfare across 22 societies

Students from 22 nations answered a survey on the most important events in world history. At the national level, free recalling and a positive evaluation of World War II (WWII) were associated with World Values Survey willingness to fight for the country in a war and being a victorious nation. Willingness to fight, a more benign evaluation of WWII, and recall of WWII were associ- ated with nation-level scores on power distance and low postmaterialism, suggesting that values stressing obedience and competition between nations are associated with support for collective violence, whereas values of expressive individualism are negatively related. Internal political vio- lence was unrelated to willingness to fight, excluding direct learning as an explanation of legit- imization of violence. Recall of wars in general (operationalized by WWI recall) was also unrelated to willingness to fight. Results replicate and extend Archer and Gartner’s classic study showing the legitimization of violence by war to the domain of collective remembering

Certolizumab Pegol for Treating Rheumatoid Arthritis Following Inadequate Response to a TNF-α Inhibitor: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (UCB Pharma) of certolizumab pegol (CZP; Cimzia(®)) to submit evidence of its clinical and cost effectiveness for the treatment of rheumatoid arthritis (RA) following inadequate response to a tumour necrosis factor-α inhibitor (TNFi). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a detailed review of the evidence for the clinical and cost effectiveness of the technology, based upon the company's submission to NICE. The clinical effectiveness evidence in the company's submission for CZP was based predominantly on six randomised controlled trials (RCTs) comparing the efficacy of CZP against placebo. The clinical effectiveness review identified no head-to-head evidence on the efficacy of CZP against the comparators within the scope; therefore, the company performed a network meta-analysis (NMA). The company's NMA concluded that CZP had a similar efficacy to that of its comparators. The company submitted a Markov model that assessed the incremental cost effectiveness of CZP versus comparator biologic disease-modifying antirheumatic drugs (bDMARDs) for the treatment of RA from the perspective of the National Health Service for three decision problems, each of which followed an inadequate response to a TNFi. These were (1) a comparison against rituximab (RTX) in combination with methotrexate (MTX); (2) a comparison against bDMARDs when RTX was contraindicated or withdrawn due to an adverse event; and (3) a comparison against bDMARDs when MTX was contraindicated or withdrawn due to an adverse event. Results from the company's economic evaluation showed that CZP resulted in a similar number of quality-adjusted life years (QALYs) produced at similar or lower costs compared with comparator bDMARDs. The commercial-in-confidence patient access schemes for abatacept and tocilizumab could not be incorporated by the company, but were incorporated by the ERG in a confidential appendix for the NICE Appraisal Committee (AC). The company estimated that the addition of CZP before RTX in a sequence for patients who could receive MTX produced more QALYs at an increased cost, with a cost per QALY of £33,222. Following a critique of the model, the ERG undertook exploratory analyses that did not change the conclusions reached based on the company's economic evaluation in relation to the comparison with bDMARDs. The ERG estimated that where CZP replaced RTX, CZP was dominated, as it produced fewer QALYs at an increased cost. The AC concluded that there was little difference in effectiveness between CZP and comparator bDMARDs and that equivalence among bDMARDs could be accepted. The AC consequently recommended CZP plus MTX for people for whom RTX is contraindicated or not tolerated and CZP monotherapy for people for whom MTX is contraindicated or not tolerated. The AC concluded that CZP plus MTX could not be considered a cost-effective use of National Health Service resources when RTX plus MTX is a treatment option

A dinuclear ruthenium(II) complex excited by near-infrared light through two-photon absorption induces phototoxicity deep within hypoxic regions of melanoma cancer spheroids

The dinuclear photo-oxidizing RuII complex [{Ru(TAP2)}2(tpphz)]4+ (TAP = 1,4,5,8- tetraazaphenanthrene, tpphz = tetrapyrido[3,2-a:2',3'-c:3'',2''- h:2''',3'''-j]phenazine), 14+ is readily taken up by live cells localizing in mitochondria and nuclei. In this study, the two-photon absorption cross-section of 14+ is quantified and its use as a two-photon absorbing phototherapeutic is reported. It was con-firmed that the complex is readily photo-excited using near infrared, NIR, light through two-photon absorption, TPA. In 2-D cell cul-tures, irradiation with NIR light at low power results in precisely focused photo-toxicity effects in which human melanoma cells were killed after 5 minutes of light exposure. Similar experiments were then carried out in human cancer spheroidsthat provide a realistic tumor model for the development of therapeutics and phototherapeutics. Using the characteristic emission of the complex as a probe, its up-take into 280 µm spheroids was investigated and confirmed that the spheroid takes up the complex. Notably TPA excitation results in more intense luminescence being observed throughout the depth of the spheroids, although emission intensity still drops off toward the necrotic core. As 14+ can directly photo-oxidize DNA without the mediation of singlet oxygen or other reactive oxygen species, photo-toxicity within the deeper, hypoxic layers of the spheroids was also investigated. To quantify the penetration of these phototoxic effects, 14+ was photo-excited through TPA at a power of 60 mW, which was progressively focused in 10 µm steps throughout the entire z-axis of individual spheroids. These experiments revealed that, in irradiated spheroids treated with 14+, acute and rapid photo-induced cell death was observed throughout their depth, including the hypoxic region

Certolizumab Pegol for Treating Rheumatoid Arthritis Following Inadequate Response to a TNF-α Inhibitor: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (UCB Pharma) of certolizumab pegol (CZP; Cimzia(®)) to submit evidence of its clinical and cost effectiveness for the treatment of rheumatoid arthritis (RA) following inadequate response to a tumour necrosis factor-α inhibitor (TNFi). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a detailed review of the evidence for the clinical and cost effectiveness of the technology, based upon the company's submission to NICE. The clinical effectiveness evidence in the company's submission for CZP was based predominantly on six randomised controlled trials (RCTs) comparing the efficacy of CZP against placebo. The clinical effectiveness review identified no head-to-head evidence on the efficacy of CZP against the comparators within the scope; therefore, the company performed a network meta-analysis (NMA). The company's NMA concluded that CZP had a similar efficacy to that of its comparators. The company submitted a Markov model that assessed the incremental cost effectiveness of CZP versus comparator biologic disease-modifying antirheumatic drugs (bDMARDs) for the treatment of RA from the perspective of the National Health Service for three decision problems, each of which followed an inadequate response to a TNFi. These were (1) a comparison against rituximab (RTX) in combination with methotrexate (MTX); (2) a comparison against bDMARDs when RTX was contraindicated or withdrawn due to an adverse event; and (3) a comparison against bDMARDs when MTX was contraindicated or withdrawn due to an adverse event. Results from the company's economic evaluation showed that CZP resulted in a similar number of quality-adjusted life years (QALYs) produced at similar or lower costs compared with comparator bDMARDs. The commercial-in-confidence patient access schemes for abatacept and tocilizumab could not be incorporated by the company, but were incorporated by the ERG in a confidential appendix for the NICE Appraisal Committee (AC). The company estimated that the addition of CZP before RTX in a sequence for patients who could receive MTX produced more QALYs at an increased cost, with a cost per QALY of £33,222. Following a critique of the model, the ERG undertook exploratory analyses that did not change the conclusions reached based on the company's economic evaluation in relation to the comparison with bDMARDs. The ERG estimated that where CZP replaced RTX, CZP was dominated, as it produced fewer QALYs at an increased cost. The AC concluded that there was little difference in effectiveness between CZP and comparator bDMARDs and that equivalence among bDMARDs could be accepted. The AC consequently recommended CZP plus MTX for people for whom RTX is contraindicated or not tolerated and CZP monotherapy for people for whom MTX is contraindicated or not tolerated. The AC concluded that CZP plus MTX could not be considered a cost-effective use of National Health Service resources when RTX plus MTX is a treatment option

Rheumatoid arthritis treated with 6-months of first-line biologic or biosimilar therapy: an updated systematic review and network meta-analysis.

OBJECTIVES: The aim of this study was to estimate the effectiveness of first-line biologic disease modifying drugs(boDMARDs), and their approved biosimilars (bsDMARDs), compared with conventional (csDMARD) treatment, in terms of ACR (American College of Rheumatology) and EULAR (European League against Rheumatism) responses. METHODS: Systematic literature search, on eight databases to January 2017, sought ACR and EULAR data from randomized controlled trials (RCTs) of boDMARDs / bsDMARDs (in combination with csDMARDs, or monotherapy). Two adult populations: methotrexate (MTX)-naïve patients with severe active RA; and csDMARD-experienced patients with moderate-to-severe active RA. Network meta-analyses (NMA) were conducted using a Bayesian Markov chain Monte Carlo simulation using a random effects model with a probit link function for ordered categorical. RESULTS: Forty-six RCTs met the eligibility criteria. In the MTX-naïve severe active RA population, no biosimilar trials meeting the inclusion criteria were identified. MTX plus methylprednisolone (MP) was most likely to achieve the best ACR response. There was insufficient evidence that combination boDMARDs was superior to intensive (two or more) csDMARDs. In the csDMARD-experienced, moderate-to-severe RA population, the greatest effects for ACR responses were associated with tocilizumab (TCZ) monotherapy, and combination therapy (plus MTX) with bsDMARD etanercept (ETN) SB4, boDMARD ETN and TCZ. These treatments also had the greatest effects on EULAR responses. No clear differences were found between the boDMARDs and their bsDMARDs. CONCLUSIONS: In MTX-naïve patients, there was insufficient evidence that combination boDMARDs was superior to two or more csDMARDs. In csDMARD-experienced patients, boDMARDs and bsDMARDs were comparable and all combination boDMARDs / bsDMARDs were superior to single csDMARD

The cost-effectiveness of sequences of biological disease-modifying antirheumatic drug treatment in England for patients with rheumatoid arthritis who can tolerate methotrexate.

Objective: To ascertain whether strategies of treatment with a biological diseasemodifying antirheumatic drug (bDMARD) were cost-effective in an English setting. Results are presented for those patients with moderate-to-severe rheumatoid arthritis (RA) and those with severe RA. Methods: An economic model to assess the cost-effectiveness of seven bDMARDs was developed. A systematic literature review and network meta-analysis was undertaken to establish relative clinical effectiveness. The results together with estimates of: Health Assessment Questionnaire (HAQ) score following European League Against Rheumatism response; annual costs, and utility, per HAQ band; trajectory of HAQ for patients on bDMARDs; and trajectory of HAQ for patients on non-biologic therapy (NBT) were used to populate the model. Results were presented as those associated with the strategy with the median cost-effectiveness. Supplementary analyses were undertaken assessing the change in cost-effectiveness where only patients with the most severe prognoses on NBT were provided with bDMARD treatment. The cost per QALY values were compared with reported thresholds from the National Institute for Health and Care Excellence of £20,000 to £30,000. Results: In the primary analyses, the cost per QALY of a bDMARD strategy was £41,600 for patients with severe RA and £51,100 for those with moderate-to-severe RA. Under the supplementary analyses the cost per QALY fell to £25,300 for those with severe RA and to £28,500 for those with moderate-to-severe RA. Conclusion: The cost-effectiveness of bDMARDs in RA in England is questionable and only meets current accepted levels in subsets of patients with the worst prognoses

The Narrative Frame of Daniel: A Literary Assessment

This paper presents a fuzzy multicriteria group decision making approach for evaluating and selecting information systems projects. The inherent subjectiveness and imprecision of the evaluation process is modeled by using linguistic terms characterized by triangular fuzzy numbers. A new algorithm based on the concept of the degree of dominance is developed to avoid the complex and unreliable process of comparing fuzzy numbers usually required in fuzzy multicriteria decision making. A multicriteria decision support system is proposed to facilitate the evaluation and selection process. An information systems project selection problem is presented to demonstrate the effectiveness of the approach

Recent Developments in Modeling Heteroepitaxy/Heterogeneous Nucleation by Dynamical Density Functional Theory

Crystallization of supersaturated liquids usually starts by epitaxial growth or by heterogeneous nucleation on foreign surfaces. Herein, we review recent advances made in modeling heteroepitaxy and heterogeneous nucleation on flat/modulated surfaces and nanoparticles within the framework of a simple dynamical density functional theory, known as the phase-field crystal model. It will be shown that the contact angle and the nucleation barrier are nonmonotonous functions of the lattice mismatch between the substrate and the crystalline phase. In continuous cooling studies for substrates with lattice mismatch, we recover qualitatively the Matthews–Blakeslee mechanism of stress release via the misfit dislocations. The simulations performed for particle-induced freezing will be confronted with recent analytical results, exploring thus the validity range of the latter. It will be demonstrated that time-dependent studies are essential, as investigations based on equilibrium properties often cannot identify the preferred nucleation pathways. Modeling of these phenomena is essential for designing materials on the basis of controlled nucleation and/or nano-patterning