Visual parameter optimisation for biomedical image processing

Background: Biomedical image processing methods require users to optimise input parameters to ensure high quality output. This presents two challenges. First, it is difficult to optimise multiple input parameters for multiple input images. Second, it is difficult to achieve an understanding of underlying algorithms, in particular, relationships between input and output. Results: We present a visualisation method that transforms users’ ability to understand algorithm behaviour by integrating input and output, and by supporting exploration of their relationships. We discuss its application to a colour deconvolution technique for stained histology images and show how it enabled a domain expert to identify suitable parameter values for the deconvolution of two types of images, and metrics to quantify deconvolution performance. It also enabled a breakthrough in understanding by invalidating an underlying assumption about the algorithm. Conclusions: The visualisation method presented here provides analysis capability for multiple inputs and outputs in biomedical image processing that is not supported by previous analysis software. The analysis supported by our method is not feasible with conventional trial-and-error approaches

Learning from Sustainability-Oriented Innovation

This chapter argues that insights from the realm of sustainability-oriented innovation can provide useful answers to the question of why Small and Medium-Sized Enterprises (SMEs) would (or should) become interested in implementing responsible innovation practices. It is based on the assumption that “responsible innovation” and “sustainability-oriented innovation” are different approaches aimed at orienting innovation towards increased positive impacts on social and natural environments. Motivations and influences for pursuing sustainability-oriented inno-vation have been studied in the past, and can provide insights into reasons for pursu-ing the implementation of responsible innovation practices

Analysis of trastuzumab and chemotherapy in advanced breast cancer after the failure of at least one earlier combination: An observational study

BACKGROUND: Combining trastuzumab and chemotherapy is standard in her2/neu overexpressing advanced breast cancer. It is not established however, whether trastuzumab treatment should continue after the failure of one earlier combination. In this trial, we report our experience with continued treatment beyond disease progression. METHODS: Fifty-four patients, median age 46 years, range 25–73 years, were included. We analysed for time to tumour progression (TTP) for first, second and beyond second line treatment, response rates and overall survival. RESULTS: Median time of observation was 24 months, range 7–51. Response rates for first line treatment were 7.4% complete remission (CR), 35.2% partial remissions (PR), 42.6% stable disease > 6 months (SD) and 14.8% of patients experienced disease progression despite treatment (PD). Corresponding numbers for second line were 3.7% CR, 22.2% PR, 42.6% SD and 31.5% PD; numbers for treatment beyond second line (60 therapies, 33 pts 3(rd )line, 18 pts 4(th )line, 6 pts 5(th )line, 2 pts 6(th )line and 1 patient 7(th )line) were 1.7% CR, 28.3% PR, 28.3% SD and 41.6% PD respectively. Median TTP was 6 months (m) in the first line setting, and also 6 m for second line and beyond second line. An asymptomatic drop of left ventricular ejection fraction below 50% was observed in one patient. No case of symptomatic congestive heart failure was observed. CONCLUSION: The data presented clearly strengthen evidence that patients do profit from continued trastuzumab treatment. The fact that TTP did not decrease significantly from first line to beyond second line treatment is especially noteworthy. Still, randomized trials are warranted

Compressive properties of min-mod-type limiters in modelling shockwave-containing flows

The long-ignored compressive properties of Min-mod-type limiter is investigated in this manuscript by demonstrating its potential in numerically modelling shockwave-containing flows, especially in shock wave/boundary layer interaction (SWBLI) problems. Theoretical studies were firstly performed based on Sweby’s total variation diminishing (TVD) limiter region and Spekreijse’s monotonicity-preserving limiter region to indicate Min-mod-type limiters’ compressive properties. The influence of limiters on the solution accuracy was evaluated using a hybrid-order analysis method based on the grid-independent study in three typical shockwave-containing flows. The conclusions are that, Min-mod-type limiter can be utilized as a dissipative and/or compressive limiter, but depending on the reasonable value of the compression parameter. The compressive Min-mod limiter tends to be more attractive in modelling shockwave-containing flows as compared to other commonly preferred limiters because of its stable computational process and its high-resolution predictions. However, the compressive Min-mod limiter may suffer from its slightly poor convergence, as that observed in other commonly accepted smooth limiters in modelling SWBLI problems. © 2020, The Author(s)

A prospective randomised trial to study the role of levamisole and interferon alfa in an adjuvant therapy with 5-FU for stage III colon cancer

The purpose of this trial was to examine the efficacy of the addition of levamisole (LEV) or interferon alfa (IFN) to an adjuvant chemotherapy with 5-fluorouracil (5-FU) in patients with stage III colon cancer. According to a 2 × 2 factorial study design, 598 patients were randomly assigned to one of four adjuvant treatment arms. Patients in arm one received 5-FU weekly for 1 year, patients in arm two 5-FU plus LEV, in arm three 5-FU plus IFN and patients in arm four 5-FU, LEV and IFN. The relative risk of relapse and the relative risk of death were significantly higher for patients treated with LEV compared with those without LEV treatment (HR 1.452, 95% CI 1.135–1.856, P=0.0028; HR 1.506, 95% CI 1.150–1.973, P=0.0027, respectively). No significant impact on survival was observed for therapy with IFN in the univariate analysis. The addition of LEV to adjuvant 5-FU significantly worsened the prognosis of patients with stage III colon cancer. Interferon alfa had no significant influence on survival when combined with adjuvant 5-FU, but increased the toxicity of therapy substantially

Identifying and prioritizing strategies for comprehensive liver cancer control in Asia

<p>Abstract</p> <p>Background</p> <p>Liver cancer is both common and burdensome in Asia. Effective liver cancer control, however, is hindered by a complex etiology and a lack of coordination across clinical disciplines. We sought to identify strategies for inclusion in a comprehensive liver cancer control for Asia and to compare qualitative and quantitative methods for prioritization.</p> <p>Methods</p> <p>Qualitative interviews (N = 20) with international liver cancer experts were used to identify strategies using Interpretative Phenomenological Analysis and to formulate an initial prioritization through frequency analysis. Conjoint analysis, a quantitative stated-preference method, was then applied among Asian liver cancer experts (N = 20) who completed 12 choice tasks that divided these strategies into two mutually exclusive and exhaustive subsets. Respondents' preferred plan was the primary outcome in a choice model, estimated using ordinary least squares (OLS) and logistic regression. Priorities were then compared using Spearman's Rho.</p> <p>Results</p> <p>Eleven strategies were identified: <it>Access to treatments; Centers of excellence; Clinical education; Measuring social burden; Monitoring of at-risk populations; Multidisciplinary management; National guidelines; Public awareness; Research infrastructure; Risk-assessment and referral</it>; and <it>Transplantation infrastructure</it>. Qualitative frequency analysis indicated that <it>Risk-assessment and referral </it>(85%), <it>National guidelines </it>(80%) and <it>Monitoring of at-risk populations </it>(80%) received the highest priority, while conjoint analysis pointed to <it>Monitoring of at-risk populations </it>(p < 0.001), <it>Centers of excellence </it>(p = 0.002), and <it>Access to treatments </it>(p = 0.004) as priorities, while <it>Risk-assessment and referral </it>was the lowest priority (p = 0.645). We find moderate concordance between the qualitative and quantitative methods (rho = 0.20), albeit insignificant (p = 0.554), and a strong concordance between the OLS and logistic regressions (rho = 0.979; p < 0.0001).</p> <p>Conclusions</p> <p>Identified strategies can be conceptualized as the ABCs of comprehensive liver cancer control as they focus on <it>Antecedents</it>, <it>Better care </it>and <it>Connections </it>within a national strategy. Some concordance was found between the qualitative and quantitative methods (e.g. <it>Monitoring of at-risk populations</it>), but substantial differences were also identified (e.g. qualitative methods gave highest priority to risk-assessment and referral, but it was the lowest for the quantitative methods), which may be attributed to differences between the methods and study populations, and potential framing effects in choice tasks. Continued research will provide more generalizable estimates of priorities and account for variation across stakeholders and countries.</p

Different rates of spontaneous mutation of chloroplastic and nuclear viroids as determined by high-fidelity ultra-deep sequencing

[EN] Mutation rates vary by orders of magnitude across biological systems, being higher for simpler genomes. The simplest known genomes correspond to viroids, subviral plant replicons constituted by circular non-coding RNAs of few hundred bases. Previous work has revealed an extremely high mutation rate for chrysanthemum chlorotic mottle viroid, a chloroplastreplicating viroid. However, whether this is a general feature of viroids remains unclear. Here, we have used high-fidelity ultra-deep sequencing to determine the mutation rate in a common host (eggplant) of two viroids, each representative of one family: the chloroplastic eggplant latent viroid (ELVd, Avsunviroidae) and the nuclear potato spindle tuber viroid (PSTVd, Pospiviroidae). This revealed higher mutation frequencies in ELVd than in PSTVd, as well as marked differences in the types of mutations produced. Rates of spontaneous mutation, quantified in vivo using the lethal mutation method, ranged from 1/1000 to 1/800 for ELVd and from 1/7000 to 1/3800 for PSTVd depending on sequencing run. These results suggest that extremely high mutability is a common feature of chloroplastic viroids, whereas the mutation rates of PSTVd and potentially other nuclear viroids appear significantly lower and closer to those of some RNA viruses.This work was supported by the European Research Council (erc.europa.eu; ERC-2011-StG-281191-VIRMUT to RS), the Spanish Ministerio de Economia y Competitividad (www.mineco.gob.es; BFU2013-41329 grant to RS, BFU2014-56812-P grant to RF, and a predoctoral fellowship to ALC), and the Spanish Junta de Comunidades de Castilla-La Mancha (www.castillalamancha.es;postdoctoral fellowship to CB). 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Meaning in Life as a Mediator of Ethnic Identity and Adjustment Among Adolescents from Latin, Asian, and European American Backgrounds

Establishing a sense of life meaning is a primary facet of well-being, yet is understudied in adolescent development. Using data from 579 adolescents (53% female) from Latin American, Asian, and European backgrounds, demographic differences in meaning in life, links with psychological and academic adjustment, and the role of meaning in explaining associations between ethnic identity and adjustment were examined. Although no generational or gender differences were found, Asian Americans reported higher search for meaning than Latin and European Americans. Presence of meaning was positively associated with self-esteem, academic adjustment, daily well-being, and ethnic belonging and exploration, whereas search for meaning was related to lower self-esteem and less stability in daily well-being. Presence of meaning mediated associations between ethnic identity and adjustment, explaining 28–52% of ethnic identity’s protective effect on development. Ethnic identity thus appears to affect adjustment, in part, through its role in fostering a positive sense of meaning in adolescents’ lives