High-Speed Real-Time Simulators for Engineering Design

The use of computer simulations is now an established technique in engineering design. Many of these simulations are used to predict the expected behavior of systems that are not yet built, or of existing systems in modes of operation, such as catastrophic failure, in which it is not feasible to test the real system. Another use of computer simulations is for training and testing purposes in which the simulation is interfaced to real hardware, software and/or a human operator and is required to operate in real-time. Examples are plant simulators for operator training or simulated environments for testing hardware or software components. The primary requirement of a real-time simulation is that it must complete all the calculations necessary to update the simulator outputs as well as all the necessary data I/O within the allotted frame time. Many real-time simulations use frame times in the range of a few milliseconds and greater.There is an increasing number of applications, for example in power electronics and automotive systems, in which much shorter frame rates are required. This paper reviews some of these applications and the approaches to real-time simulation that can achieve frame times in the range 5 to 100 microseconds.

Cost-effectiveness of the Manchester approach to identifying Lynch syndrome in women with endometrial cancer

This is the final version. Available on open access from MDPI via the DOI in this recordLynch syndrome (LS) is a hereditary cancer syndrome responsible for 3% of all endometrial cancer and 5% in those aged under 70 years. It is unclear whether universal testing for LS in endometrial cancer patients would be cost-effective. The Manchester approach to identifying LS in endometrial cancer patients uses immunohistochemistry (IHC) to detect mismatch repair (MMR) deficiency, incorporates testing for MLH1 promoter hypermethylation, and genetic testing for pathogenic MMR variants. We aimed to assess the cost-effectiveness of the Manchester approach based on primary research data from clinical practice in Manchester. The PETALS study informed estimates of diagnostic performances for a number of different strategies. A recent microcosting study was adapted and used to estimate diagnostic costs. A Markov model was used to predict long-term costs and health outcomes (measured in quality-adjusted life years, QALYs) for individuals and their relatives. Bootstrapping and probabilistic sensitivity analysis were used to estimate the uncertainty in cost-effectiveness. The Manchester approach dominated other reflex testing strategies when considering diagnostic costs and Lynch syndrome cases identified. When considering long-term costs and QALYs the Manchester approach was the optimal strategy, costing £5459 per QALY gained (compared to thresholds of £20,000 to £30,000 per QALY commonly used in the NHS). Cost-effectiveness is not an argument for restricting testing to younger patients or those with a strong family history. Universal testing for Lynch syndrome in endometrial cancer patients is expected to be cost-effective in the UK NHS, and the Manchester approach is expected to be the optimal testing strategy.Medical Research Council (MRC)National Institute for Health Research (NIHR

Conceptions of Learning and Teaching and Their Relation to Educational Variables During Teaching Second Language

Background:  People who choose to study a second language like English face an emotional charge that affects directly to the learning process. Regarding the writing production, learners create short compositions about specific topics with instructions based on grammatical structures. Once it is done, learners receive feedback on their work. However, some learners do not want to write any text because the teacher puts more attention to their mistakes rather than their successes. Without taking into account their needs, topics of interest or motivation for carrying out the exercise Contribution:  Therefore, it is set to identify the emotions that are generated by the corrections made to our learners’ written work. Method:  The research was carried on with university students aged between 18 and 25 years old who are attending classes at the center of university language classroom. This research during the April- August 2016 term. Results: It has been found that the emotions (positive and negative) play an important role or have a great impact that causes aversion towards language learning. Therefore, it is necessary that teachers provide adequate feedback for language learning. Conclusion:  Corrections generate aversion towards the learning process. Regarding the feedback students receive from their teachers, it generates emotional charge (positive and negative) which should be followe

Histological and Somatic Mutational Profiles of Mismatch Repair Deficient Endometrial Tumours of Different Aetiologies

SIMPLE SUMMARY: Endometrial cancers can arise due to an error in DNA mending known as mismatch repair. This can happen because of an error in the cancer itself (somatic) or due to an inherited error (Lynch syndrome). Treatment trials have considered endometrial cancers caused by either of these errors as identical. As it is easier to recruit people with Lynch syndrome, they may be overrepresented in this group despite being less numerous in clinical practice. This would not be an issue if somatic and Lynch syndrome-related endometrial cancers were similar at a molecular level. The data presented herein, however, indicates that these two routes to mismatch repair, although sharing many similarities, lead to endometrial cancers with distinct molecular and pathological features. This may explain the range of outcomes observed in clinical trials of endometrial cancers with mismatch repair errors. ABSTRACT: Background: Mismatch repair deficient (MMRd) tumours may arise from somatic events acquired during carcinogenesis or in the context of Lynch syndrome (LS), an inherited cancer predisposition condition caused by germline MMR pathogenic variants. Our aim was to explore whether sporadic and hereditary MMRd endometrial cancers (EC) display distinctive tumour biology. Methods: Clinically annotated LS-EC were collected. Histological slide review was performed centrally by two specialist gynaecological pathologists. Mutational analysis was by a bespoke 75- gene next-generation sequencing panel. Comparisons were made with sporadic MMRd EC. Multiple correspondence analysis was used to explore similarities and differences between the cohorts. Results: After exclusions, 135 LS-EC underwent independent histological review, and 64 underwent mutational analysis. Comparisons were made with 59 sporadic MMRd EC. Most tumours were of endometrioid histological subtype (92% LS-EC and 100% sporadic MMRd EC, respectively, p = NS). Sporadic MMRd tumours had significantly fewer tumour infiltrating lymphocytes (p ≤ 0.0001) and showed more squamous/mucinous differentiation than LS-EC (p = 0.04/p = 0.05). PTEN mutations were found in 88% sporadic MMRd and 61% LS-EC, respectively (p < 0.001). Sporadic MMRd tumours had significantly more mutations in PDGFRA, ALK, IDH1, CARD11, CIC, MED12, CCND1, PTPN11, RB1 and KRAS, while LS-EC showed more mutations affecting SMAD4 and ARAF. LS-EC showed a propensity for TGF-β signalling disruption. Cluster analysis found that wild type PTEN associates predominantly with LS-EC, whilst co-occurring mutations in PTEN, PIK3CA and KRAS predict sporadic MMRd EC. Conclusions: Whilst MMRd EC of hereditary and sporadic aetiology may be difficult to distinguish by histology alone, differences in infiltrating immune cell counts and mutational profile may predict heterogenous responses to novel targeted therapies and warrant further study

DNA damage and repair kinetics after microbeam radiation therapy emulation in living cells using monoenergetic synchrotron X-ray microbeams

The molecular response of mammalian cells to a monoenergetic synchrotron X-ray microbeam which emulated microbeam radiation configurations has been investigated. Very few γH2AX foci were found outside the irradiated zone within 1 h of irradiation, even within a single nucleus. Furthermore, 12 h after radiation there was a large decrease in foci number but many cells still contained γH2AX foci, of which many were outside the directly irradiated regions

Energy Dependence of Nuclear Transparency in C(p,2p) Scattering

The transparency of carbon for (p,2p) quasi-elastic events was measured at beam energies ranging from 6 to 14.5 GeV at 90 degrees c.m. The four momentum transfer squared q*q ranged from 4.8 to 16.9 (GeV/c)**2. We present the observed energy dependence of the ratio of the carbon to hydrogen cross sections. We also apply a model for the nuclear momentum distribution of carbon to normalize this transparency ratio. We find a sharp rise in transparency as the beam energy is increased to 9 GeV and a reduction to approximately the Glauber level at higher energies.Comment: 4 pages, 2figures, submitted to PR

Default Risk and Equity Returns: A Comparison of the Bank-Based German and the U.S. Financial System

In this paper, we address the question whether the impact of default risk on equity returns depends on the financial system firms operate in. Using an implementation of Merton's option-pricing model for the value of equity to estimate firms' default risk, we construct a factor that measures the excess return of firms with low default risk over firms with high default risk. We then compare results from asset pricing tests for the German and the U.S. stock markets. Since Germany is the prime example of a bank-based financial system, where debt is supposedly a major instrument of corporate governance, we expect that a systematic default risk effect on equity returns should be more pronounced for German rather than U.S. firms. Our evidence suggests that a higher firm default risk systematically leads to lower returns in both capital markets. This contradicts some previous results for the U.S. by Vassalou/Xing (2004), but we show that their default risk factor looses its explanatory power if one includes a default risk factor measured as a factor mimicking portfolio. It further turns out that the composition of corporate debt affects equity returns in Germany. Firms' default risk sensitivities are attenuated the more a firm depends on bank debt financing