Revista Jurídica Digital UANDES
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In defence of existence questions
No full textDo numbers exist? Do properties? Do possible worlds? Do fictional characters? Many metaphysicians spend time and effort trying to answer these and other questions about the existence of various entities. These inquiries have recently encountered opposition: a group of philosophers, drawing inspiration from Aristotle, have argued that many or all of the existence questions debated by metaphysicians can be answered trivially, and so are not worth debating. Our task is to defend existence questions from the neo-Aristotelians' attacks
Evaluation of ballistic performance of STF impregnated fabrics under high velocity impact
No full textShear thickening fluid (STF) impregnated fabrics offer improved ballistic performance against impacts, but the effect becomes not obvious at high impact velocity (e.g. 300m/s) as reported by some. This paper presents findings from an investigation of STF-impregnated fabric panels against ballistic impact, and attempts to identify the failure mechanisms of such panels under high velocity impact, which will shed light on effects of STF-impregnated fabrics for low and high velocity impacts. Single-ply and 10-ply neat and STF-impregnated aramid fabric panels were experimented on at impact velocities around 500m/s. The results indicated that the specific energy absorption of the single-ply and 10-ply STF impregnated fabric panels was 44.8% and 64.1% lower than that of their neat counterparts respectively. The mechanisms were studied theoretically and morphologically. It was found that the projectile velocities perforating the fabrics were decreased by STF impregnation due to the total movement constraint of the primary yarns. This changes the failure mode from tensile dominant to shear dominant, increases the possibility of earlier damage and failure of the primary yarns, and reduces the pull out distance, causing decrease in the energy absorption. The findings are significant for guiding further design of STF impregnated fabric panels for ballistic protection
Value assessment and quantitative benefit-risk modelling of biosimilar infliximab for Crohn’s disease
No full textAim: Regulatory approval of biosimilars often depends on extrapolating evidence from one clinical indication to all of those of the originator biologic. We aimed to develop a quantitative benefit-risk analysis to assess whether the resulting increase in the uncertainty in the clinical performance of biosimilars (i.e. risk) may be countered by their lower pricing (benefit).Methods: A one-year decision-analytic model was developed for the biosimilar infliximab (Inflectra®) for Crohn’s disease. The perspective was that of the NHS in the UK and costs were valued to 2015/16. A hypothetical cohort of biologic-naïve patients with moderate-to-severe Crohn’s disease were simulated through the model. Immunogenicity to infliximab was a key modifier, influencing rates of non-response and infusion reactions. Net health benefit was estimated based on quality-adjusted life years (QALYs). A range of sensitivity analyses tested the robustness of the results and explored how the biosimilar price must respond to varying immunogenicity to remain the preferred option. Results: The base-case analysis predicted a positive incremental net health benefit of 0.04 (95% Central Range 0.00-0.09) favouring the biosimilar, based on 0.803 QALYs, and costs of £18,087 and £19,176 for biosimilar and originator, respectively. Two-way sensitivity analyses suggested that if 50% of patients developed antibodies, the value-based price of £410 per vial must be lower than that of the originator (£420), but remain higher than the actual market price (£378). Conclusions: The model supports the use of Inflecta® for Crohn’s disease in the UK, and provides a framework for the quantitative evaluation of biosimilars in the context of health technology assessment. Value-based pricing using this methodology could protect health systems from the potential risks of biosimilars where they are untested in the approved populations.<br/
Donor insulin therapy predicts early graft outcomes in pancreas and islet transplantation
No full textIntroduction: Organ donors frequently develop hyperglycaemia, which is managed with insulin on intensive care. It is unclear what proportion of this hyperglycaemia is caused by reversible insulin resistance and how much is caused by beta-cell death. We hypothesised that Donor Insulin Use (DIU) on intensive care is a predictor of pancreas and islet transplant outcomes.Methods: Data on organ donors from the United Kingdom (UK) Transplant Registry was linked with regional data from our solid organ pancreas transplant (SPT) programme (2010-2015) and with national data from the UK Islet Transplant Consortium (2008-2016). Regression models determined associations between DIU and 3-month graft function and survival. Results: In 168 SPT recipients, DIR was associated with a higher rate of early graft loss from non-technical failure (failure rate: DIR vs. no-DIR: 6/71 [8.5%] vs 1/97 (1.0%], odds ratio, 95% CI: 8.9, 1.04-75.3, p=0.046) and lower 72-hours post-transplantation c-peptide (n=46; DIU vs. no-DIR: 1431 (1117) vs. 2496 (1702) pmol/L, p=0.005). In 91 islet cell transplant (ICT) recipients, DIR was associated with a higher 3-month HbA1c (n=74; DIU vs. no-DIU: 51 (15) vs. 45 (9) mmol/mol, p=0.044) and a higher 90-minute stimulated glucose levels (n=74, 15.9 (6.3) vs. 12.7 (4.3) mmol/l, p=0.012). Conclusion: In SPT and ICT recipients, DIU in intensive care is adversely related to measures of graft loss and function. Clinicians should be aware that DIU could be a marker of beta-cell death in donor pancreata. However, it would be premature to change clinical practice based on these preliminary data. Further research is required to; a) assess whether DIU can improve the prediction of graft outcomes; and b) develop objective tests of beta-cell death in potential donor pancreata. <br/
Elevated local senescence in diabetic wound healing is linked to pathological repair via CXCR2
No full textCellular senescence can be broadly defined as a stable, but essentially irreversible, loss of proliferative capacity. Historically, senescence has been described as a negative outcome of advanced cellular age. It is now clear, however, that senescence represents a dynamic autonomous stress response, integral to long-term tumor suppression. Transient induction of a senescent phenotype has actually been suggested to promote regeneration in both liver and skin. Here, we explored the role of senescence in pathological aged and diabetic murine wound healing. Aged and diabetic wounds had greater numbers of senescent cells, and diabetic macrophages maintained altered retention of polarization and produced a CXCR2-enriched senescence-associated secretory phenotype (i.e., SASP). Of translational relevance, targeted expression of CXCR2 in primary human dermal fibroblasts led to paracrine induction of nuclear p21. Furthermore, a selective agonist to CXCR2 was able to reverse delayed healing in diabetic mice and accelerate ex vivo human skin wound healing. Collectively, these data suggest a hitherto unappreciated role for CXCR2 in mediating cellular senescence in pathological wound repair.</p
Verication-Led Smart Contracts
No full textTuring complete smart contract formalisms (e.g. Solidity)are conceptually appealing, but leave the door open to the problems ofverifying completely arbitrary code, a task which can be of arbitrarilyhigh complexity or can be undecidable. We argue that a more structuredapproach, in which smart contract families are designed ab initio withefficient veriability in mind, provide a much more practical way for-ward. We emphasise that the boundary between on-chain and off-chaininformation, which must always be determined in an application specicmanner, is crucial in determining the practicability of smart contractverification. We discuss the role of refinement technologies in breakingdown the complexity of smart contract verification, and illustrate theargument using the Event-B formal modelling framework and Solidityas implementation vehicle
Aromatic Polyphosphonates with Ultra-High Refractive Indices
No full textHighly refractive and transparent polyphosphonates with varying aromatic backbones have been synthesised by polycondensation of phosphonic dichlorides and diols. The polyphosphonates display excellent thermal properties, with most thermally stable to up to 450°C. The glass transition temperatures of the polymers could be readily tuned from 41-214°C by terminating the polymer with different alcohols. The polymers synthesised also possess exceptional optical properties, with low UV cut off points and ultra-high refractive indices up to 1.70, the highest reported for this type of polymer. Most importantly, the polymers also display high Abbe numbers (≥52), the highest reported for intrinsic HRIPs, displaying an unprecedented combination of these two key optical metrics
Una caja para el Sol, hecha de casi nada: nanomateriales estructurales para fusión nuclear
No full textUno de los problemas más apremiantes de este siglo es el suministro sustentable de energía, pues actualmente más del 85% de la producción de energía primaria en el mundo se origina a partir de combustibles fósiles. Sin embargo, el número de candidatos no fósiles concebibles que los podrían reemplazar es muy limitado: energías renovables, fisión y fusión nuclear. En particular, el desarrollo de la tecnología de fusión nuclear, proceso mediante el cual el Sol y las estrellas generan su energía, se está desarrollando para producir energía eléctrica de manera controlada y sostenible en la Tierra. La fusión será segura al no producir desechos radiactivos, ecológicamente atractiva y su combustible, el deuterio, existe en cantidad suficiente en el agua ordinaria como para satisfacer las necesidades de energía eléctrica del mundo a la tasa actual de consumo durante millones de años. Sin embargo, los retos científicos y tecnológicos para construir y poner en operación un reactor de fusión nuclear son complejos, y su desarrollo lleva más de siete décadas de esfuerzo a nivel internacional. Tal como dijo el laureado con el premio Nobel de Física, Pierre-Gilles de Gennes, sobre la fusión nuclear: Decimos que pondremos el Sol en una caja. La idea es hermosa, el problema está en que no sabemos cómo, ni de qué hacer la caja. En este trabajo se revisan los conceptos fundamentales y los desafíos actuales alrededor de la fusión nuclear, y a continuación se describen algunos de los nuevos materiales avanzados propuestos para la construcción de reactores de fusión, en especial los que se usarían cerca de la cámara de combustible, que permitirán en principio contener el poder energético del Sol en una caja
Effect of Electric Field Uniformity on Positive Streamer and Breakdown Characteristics of Transformer Liquids
No full textStreamer development in liquid has different dominant mechanisms under uniform and divergent electric fields, respectively initiation and propagation. This paper presents a study on the influence of electric field uniformity on the pre-breakdown and breakdown characteristics of transformer insulating liquids. Streamers were investigated experimentally in different needle-plane non-uniform field and plane-needle-plane semi-uniform field configurations under standard positive lightning impulses. For the same gap distance, streamers under non-uniform field propagate with a more side-branched structure whereas streamer propagation under semi-uniform field is more constrained to the axial direction. Field enhancement factor was used to indicate the degree of inhomogeneity of the field configuration. Streamers in fields with higher field enhancement factors occupy larger areas. As field enhancement factor reduces, the streamer withstanding probability distribution gets closer to the breakdown probability distribution and hence the breakdown happens at a lower normalized voltage level. Furthermore, a transition phase from a propagation dominated to an initiation dominated process of streamer development was evident as the field enhancement factor decreases. The field enhancement factor at which this transition happens was quantitatively derived. It is 54.1 for the investigated mineral oil under positive lightning impulses
Formal Modelling and Verification as Rigorous Review Technology: An Inspiration from INSPEX
No full textReviews of various kinds are an established part of system development, but rely on the vigilance and thoroughness of the human participants for their quality. The use of formal methods as part of the toolkit deployed during review can increase those elements of dependability that formal methods do best to support. A methodology that proposes that formal techniques are used alongside conventional system construction practices during review is introduced. These can reduce the human burden of ensuring review quality, even if the coupling between the formal and conventional strands is not itself formally enforced. The approach advocated was inspired by experience of the use of formal methods in the INSPEX Project.1 This project targets the creation of a minaturised smart obstacle detection system, to be clipped onto a visually impaired or blind (VIB) person’s white cane, that would give aural feedback to the user about obstacles in front of them. The increasing complexity of such systems itself invites the use of formal techniques during development, but the hardware challenges preclude the application of textbook top-down formal methods. The use of formal methods in INSPEX is ad hoc, and the methodology proposed is an abstraction from the practical experience.<br/