Effect of fructose or sucrose feeding with different levels on oral glucose tolerance test in normal and type 2 diabetic rats

This study was designed to determine whether acute fructose or sucrose administration at different levels (0.05 g/kg, 0.1 g/kg or 0.4 g/kg body weight) might affect oral glucose tolerance test (OGTT) in normal and type 2 diabetic rats. In OGTT, there were no significant differences in glucose responses between acute fructose- and sucrose-administered groups. However, in normal rats, the AUCs of the blood glucose response for the fructose-administered groups tended to be lower than those of the control and sucrose-administered groups. The AUCs of the lower levels fructoseor sucrose-administered groups tended to be smaller than those of higher levels fructose- or sucrose-administered groups. In type 2 diabetic rats, only the AUC of the lowest level of fructose-administered (0.05 g/kg body weight) group was slightly smaller than that of the control group. The AUCs of fructose-administered groups tended to be smaller than those of the sucrose-administered groups, and the AUCs of lower levels fructose-administered groups tended to be smaller than those fed higher levels of fructose. We concluded from this experiment that fructose has tendency to be more effective in blood glucose regulation than sucrose, and moreover, that smaller amount of fructose is preferred to larger amount. Specifically, our experiments indicated that the fructose level of 0.05 g/kg body weight as dietary supplement was the most effective amount for blood glucose regulation from the pool of 0.05 g/kg, 0.1 g/kg and 0.4 g/kg body weights. Therefore, our results suggest the use of fructose as the substitute sweetener for sucrose, which may be beneficial for blood glucose regulation

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA); Scientific Opinion on Dietary Reference Values for carbohydrates and dietary fibre

This Opinion of the EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA) deals with the establishment of Dietary Reference Values for carbohydrates and dietary fibre. Nutritionally, two broad categories of carbohydrates can be differentiated: \u201cglycaemic carbohydrates\u201d, i.e. carbohydrates digested and absorbed in the human small intestine, and \u201edietary fibre\u201f, non-digestible carbohydrates passing to the large intestine. In this Opinion, dietary fibre is defined as non-digestible carbohydrates plus lignin. The absolute dietary requirement for glycaemic carbohydrates is not precisely known but will depend on the amount of fat and protein ingested. The Panel proposes 45 to 60 E% as the reference Intake range for carbohydrates applicable to both adults and children older than one year of age. Although high frequency of intake of sugar-containing foods can increase the risk of dental caries, there are insufficient data to set an upper limit for (added) sugar intake. Based on the available evidence on bowel function, the Panel considers dietary fibre intakes of 25 g/day to be adequate for normal laxation in adults. A fibre intake of 2 g/MJ is considered adequate for normal laxation in children from the age of one year. Although there is some experimental evidence that a reduction of the dietary glycaemic index and glycaemic load may have favourable effects on some metabolic risk factors such as serum lipids, the evidence for a role in weight maintenance and prevention of diet-related diseases is inconclusiv

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

OUTLIER REPORTING BY INFERENCE ON TURFS (ORBIT)

Master'sMASTER OF SCIENCE (RSH-SOC

Towards automated compliance checking in the construction industry

The Construction industry has a complex structure of regulatory compliance, consisting of statutory requirements and performance based regulations. The increasing importance of sustainability has further intensified this, with a new building’s compliance against sustainability assessment methodologies now often an important contractual requirement. Automatic compliance checking against these requirements has been long sought after within this industry and several approaches have attempted to achieve this goal. The key improvement that can be made to many existing approaches is enabling the development and maintenance of the regulations by those who are most qualified to do this the domain experts. This is illustrated by the fact that in many cases regulatory compliance systems are closed and when modifications are needed they must be made by software’s developers. This process is simply not viable in this industries rapidly changing environment. In this paper we describe our framework for compliance checking, showing the potential for utilising an integrated process to enable domain experts to create and maintain their own regulations that can then be executed by an open source rule engine. We will describe our process, the methodology and software developed to support it. We will present our initial results in the form of two case studies illustrating progress towards automation of commonly used regulations. Finally, we will also discuss how our approach could be generalised to other related sectors to enable the adoption of a similar approach towards automatic regulatory compliance

Smart interpretable model (SIM) enabling subject matter experts in rule generation

Current Artificial Intelligence (AI) technologies are widely regarded as black boxes, whose internal structures are not inherently transparent, even though they provide powerful prediction capabilities. Having a transparent model that enables users to understand its inner workings allows them to appreciate the learning and inference process, leading to trust and higher confidence in the model. While methods that help with interpretability have been created, most of them require the user to have a certain level of AI knowledge and do not allow a user to fine-tune them based on prior knowledge. In this paper, we present a smart interpretable model (SIM) framework that requires little to no AI knowledge and can be used to create a set of fuzzy IF-THEN rules along with its corresponding membership functions at ease. The framework also allows users to incorporate prior knowledge during various steps in the framework and generates comprehensive insights summarized from rules and samples, allowing users to identify anomalous rules, feature contributions of each sample and confidence level for each rule. We demonstrate these capabilities and compare our model to other existing rule-based models using various datasets that have been used for rule-based model validations. Validations are then done in terms of performance and whether the rules that are generated by SIM are similar to the rules generated by other more recent rule-based models.This study is supported under the RIE2020 Industry Alignment Fund – Industry Collaboration Projects (IAF-ICP) Funding Initiative, as well as cash and in-kind contribution from Rolls-Royce Singapore Pte Ltd

Adaptive execution of scientific workflow applications on clouds

Many e-science applications can be modeled as workflow applications. In this programming model, scientific applications are described as a set of tasks that have dependencies between them. Clouds are natural candidates for hosting such applications. This is because some of their core characteristics, such as rapid elasticity, resource pooling, and pay per use, are well suited to the nature of scientific applications that experience variable demand, spikes in resource (i.e., of the central processing unit [CPU] or disk) utilization, and sometimes, urgency for generation of results. As current workflow management systems (WfMSs) cannot support efficient and automated execution of workflow in clouds that support adaptive execution, fault tolerance, and data privacy, in this chapter we detail the requirements of a WfMS that supports these requirements, its architecture, and an application scenario involving simulation of Singapore’s public transport system