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NUC-1031 in combination with cisplatin for the first-line treatment of patients with advanced biliary tract cancer
No full textModeling past event feedback through biomarker dynamics in the multi-state event analysis for cardiovascular disease data
No full textIn cardiovascular studies, we often observe ordered multiple events along disease progression, which are essentially a series of recurrent events and terminal events with competing risk structure. One of the main interest is to explore the event specific association with the dynamics of longitudinal biomarkers. New statistical challenge arises when the biomarkers carry information from the past event history, providing feedbacks for the occurrences of future events, and particularly when these biomarkers are only intermittently observed with measurement errors. In this paper, we propose a novel modelling framework where the recurrent events and terminal events are modelled as multi-state process and the longitudinal covariates that account for event feedbacks are described by random effects models. Considering the nature of long-term observation in cardiac studies, flexible models with semiparametric coefficients are adopted. To improve computation efficiency, we develop an one-step estimator of the regression coefficients and derive their asymptotic variances for the computation of the confidence intervals, based on the proposed asymptotically unbiased estimating equation. Simulation studies show that the naive estimators which either ignore the past event feedbacks or the measurement errors are biased. Our method achieves better coverage probability, compared to the naive methods. The model is motivated and applied to a dataset from the Atherosclerosis Risk in Communities Study
Mobility and healthy ageing in the city: exploring opportunities and challenges of autonomous vehicles for older adults’ outdoor mobility
No full textOlder adults face outdoor mobility challenges due to age-related changes and problems linked to the transportation system. The advent of fully-autonomous vehicles (AVs) is expected to benefit older adults by facilitating their outdoor mobility. However, research exploring the implications of AVs from older adults’ perspective is limited. This study explores older adults’ perception of the opportunities and concerns regarding AVs, in relation to their outdoor mobility needs and challenges. Using a qualitative design, we explore these issues based on in-depth interviews conducted with participants (≥ 65 years) in Greater Manchester, UK. The results revealed that older adults perceive opportunities in AVs enhancing their physical activity, promoting social interaction and offering stress-free door-to-door mobility. They, however, expressed concerns including safety, cost, possible erosion of road etiquettes and a desirable driving culture as a result of automation, a lack of social interaction with a human driver, and possible difficulties in using AVs. The participants’ most preferred use options (i.e., public transport and shared autonomous services) are grounded in their need for social interaction, physical activity, safe and less stressful, and affordable travel. The implications of these findings for policy at the intersection of mobility and healthy ageing in future cities are discussed
Evaluating and Investigating Knowledge Management Practices and ICT in Healthcare: An Emerging Economies Perspective
No full textWe contribute by developing this special issue in the Journal of Knowledge Management, through the extension of scholarship on the role of information communication technology (ICT) in shaping knowledge management practices, specifically, in the context of healthcare, in emerging economies. In this editorial, we provide an overview of the intersection between knowledge management (KM), ICT, within the emerging economies context. This special issue includes seven key papers that take a wide variety of approaches to exploring KM and ICT in healthcare in emerging economies. These studies based on a broad range of research designs; address issues related to diverse research contexts and provide insights that help in enhancing our understanding of the phenomenon. We present a conceptual model summarizing the contribution(s) of the issue and present a critique of the papers included herein. We conclude by offering suggestions for future research and examining the generalizability of the studies included in this special issue
The Manchester perspective on using the Design Project to enhance the education of chemical engineering students
No full textThe Design Project is a major piece of work for any undergraduate in chemical engineering, enabling students to demonstrate skills and knowledge gained elsewhere in the degree programme, alongside their own abilities to create and innovate. As such, the main learning process is activity based and associated with the undertaking of an open-ended, but time limited project that poses significant challenges to most students. Particularly in the UK context, the importance of the design project is recognized via its inclusion as a separate and very significant element in the accreditation of all engineering degrees. During the past decade, developments in the Chemical Engineering Design Project at the University of Manchester have led to international recognition and prestigious awards. This perspective article aims to identify the best education practices associated with the Manchester experience and to share these to the potential benefit of programmes elsewhere. The paper includes specific details regarding the module specifications, learning outcomes, organization of the Design Project activities, individual and team work, reporting requirements, assessment procedures, and other aspects. The feedback received annually from students and fellow Design Project programme directors from other universities is also taken into account and the different perspectives are evaluated
FuSeBMC: An Energy-Efficient Test Generator for Finding Security Vulnerabilities in C Programs
No full textWe describe and evaluate a novel approach FuSeBMC that exploits fuzzing and BMC engines to detect security vulnerability in C programs. It explores and analyzes the target C program by injecting labels that guide those engines to produce test-cases. FuSeBMC also exploits selective fuzzer to produce test-cases for the labels that fuzzing and BMC engines could not produce test-cases. Lastly, we manage each engine's execution time to improve FuSeBMC's energy consumption. As a result, FuSeBMC guides the fuzzing and BMC engines to explore more profound in the target C programs and then produce test-cases that achieve higher coverage with lower energy consumption to detect bugs efficiently. We evaluated FuSeBMC by participating in Test-Comp 2021 to test the ability of the tool in two categories of the competition, which are code coverage and bug detection. The competition results show that FuSeBMC performs well if compared to the state-of-the-art software testing tools. FuSeBMC achieved 3 awards in the Test-Comp 2021: first place in the Cover-Error category, second place in the Overall category, and third place in the Low Energy Consumption
High Weissenberg number simulations with incompressible Smoothed Particle Hydrodynamics and the log-conformation formulation
No full textViscoelastic flows occur widely, and numerical simulations of them are important for a range of industrial applications. Simulations of viscoelastic flows are more challenging than their Newtonian counterparts due to the presence of exponential gradients in polymeric stress fields, which can lead to catastrophic instabilities if not carefully handled. A key development to overcome this issue is the log-conformation formulation, which has been applied to a range of numerical methods, but not previously applied to Smoothed Particle Hydrodynamics (SPH). Here we present a 2D incompressible SPH algorithm for viscoelastic flows which, for the first time, incorporates a log-conformation formulation with an elasto-viscous stress splitting (EVSS) technique. The resulting scheme enables simulations of flows at high Weissenberg numbers (accurate up to Wi=85 for Poiseuille flow). The method is robust, and able to handle both internal and free-surface flows, and a range of linear and non-linear constitutive models. Several test cases are considerd included flow past a periodic array of cylinders and jet buckling. This presents a significant step change in capabilties compared to previous SPH algorithms for viscoelastic flows, and has the potential to simulate a wide range of new and challenging applications
Prevalence and Prognosis of Lynch Syndrome and Sporadic Mismatch Repair Deficiency in Endometrial Cancer
No full textBackground: Standard screening of endometrial cancer (EC) for Lynch syndrome (LS) is gaining traction, however the prognostic impact of an underlying hereditary etiology is unknown. We established the prevalence, prognosis and subsequent primary cancer incidence of patients with LS-associated EC in relation to sporadic mismatch repair deficient (MMRd)-EC in the large combined PORTEC-1,-2 and -3 trial cohort.Methods: After MMR-immunohistochemistry, MLH1-promoter methylation testing, and next-generation sequencing, tumors were classified into three groups according to the molecular cause of their MMRd-EC. Kaplan-Meier method, log-rank test and Cox model were used for survival analysis. Competing risk analysis was used to estimate the subsequent cancer probability. All statistical tests were two-sided.Results: Among the 1336 ECs, 410 (30.7%) were MMRd. A total of 380 (92.7%) were fully triaged: 275 (72.4%) were MLH1-hypermethylated MMRd-ECs; 36 (9.5%) LS MMRd-ECs, and 69 (18.2%) MMRd-ECs due to other causes. Limiting screening of EC patients to ≤60 or ≤70 years would have resulted in missing 18 (50.0%) and 6 (16.7%) LS diagnoses. Five-year recurrence-free survival (RFS) was 91.7% (95% confidence interval [CI] = 83.1-100%; hazard ratio [HR] = 0.45, 95%CI =0.16-1.24, p=0.12) for LS, 95.5% (95% CI = 90.7-100%; HR = 0.17, 95% CI = 0.05-0.55, p=0.003) for ‘other’ versus 78.6% (95% CI = 73.8-83.7%) for MLH1-hypermethylated MMRd-EC. The probability of subsequent LS-associated cancer at 10 years was 11.6% (95%CI = 0.0-24.7%), 1.5% (95%CI = 0.0-4.3%) and 7.0% (95%CI = 3.0-10.9%) within the LS, ‘other’ and MLH1-hypermethylated MMRd-EC groups.Conclusion: The LS prevalence in the PORTEC-trial population was 2.8%, and among MMRd-ECs 9.5%. Patients with LS-associated ECs showed a trend towards better RFS and higher risk for second cancers compared to patients with MLH1-hypermethylated MMRd-EC. <br/
Parents experiences of care offered after stillbirth: International online survey of high- and middle-income countries
No full textBackground Stillbirth, the death of a baby before birth, is associated with significant psychological and social consequences that can be mitigated by respectful and supportive bereavement care. The absence of high-level evidence to support the broad scope of perinatal bereavement practices means that offering a range of options identified as valued by parents has become an important indicator of care quality. This study aimed to describe bereavement care practices offered to parents across different high- and middle-income countries. MethodsAn online survey of parents of stillborn babies was conducted between December 2014 and February 2015. Frequencies of nine practices were compared between high- and middle-income countries. Differences in proportions of reported practices and their associated odds ratios were calculated to compare high- and middle-income countries.Results Over three-thousand parents (3041) with a self-reported stillbirth in the preceding five years from 40 countries responded. At least 40 responses came from 15 countries.Significant differences in prevalence of offering nine bereavement care practices were reported by women in high-income countries (HICs) compared with women in middle-income countries MICs). All nine practices were reported to occur significantly more frequently by women in HICs, including opportunity to see and hold their baby (OR=4.8, 95%CI 4.0-5.9). Widespread occurrence of all nine practices was reported only for The Netherlands. ConclusionsBereavement care after stillbirth varies between countries. Future research should look at why these differences occur, their impact on parents, and whether differences should be addressed, particularly how to support effective communication, decision-making and follow-up care.<br/
Revascularisation strategies in patients with significant left main coronary disease during the COVID-19 pandemic
No full textBackground: There are limited data on the impact of the COVID-19 pandemic on left main (LM) coronary revascularisation activity, choice of revascularisation strategy and post-procedural outcomes.Methods: All patients with LM disease (≥50% stenosis) undergoing coronary revascularisation in England between 01/01/2017 and 19/8/2020 were included (n=22,235), stratified by time-period (pre-COVID: 01/01/2017-29/2/2020; COVID: 1/3/2020-19/8/2020) and revascularisation strategy (percutaneous coronary intervention (PCI) vs. coronary artery bypass grafting (CABG). Logistic regression models were performed to examine odds ratio (OR) of 1) receipt of CABG (vs. PCI) and 2) in-hospital and 30-day postprocedural mortality, in the COVID-19 period (vs. pre-COVID).Results: There was a decline of 1,354 LM revascularisation procedures between 1st March and 31st July 2020 compared with previous years’ (2017-2019) averages (-48.8%). An increased utilisation of PCI over CABG was observed in the COVID period (receipt of CABG vs. PCI: OR 0.46 [0.39, 0.53] compared with 2017), consistent across all age groups. No difference in adjusted in-hospital or 30-day mortality was observed between pre-COVID and COVID periods for both PCI (odds ratio (OR): 0.72 [0.51. 1.02] and 0.83 [0.62, 1.11], respectively) and CABG (OR 0.98 [0.45, 2.14] and 1.51 [0.77, 2.98], respectively) groups.Conclusion: LM revascularisation activity has significantly declined during the COVID period, with a shift towards PCI as the preferred strategy. Postprocedural mortality within each revascularisation group was similar in the pre-COVID and COVID periods, reflecting maintenance in quality of outcomes during the pandemic. Future measures are required to safely restore LM revascularisation activity to pre-COVID levels. <br/