Risk-Driven Design Processes: Balancing Efficiency with Resilience in Product Design

Current design methods and approaches focus on increasing the efficiency of the product design system by, for example, eliminating waste and focusing on value creation. However, continuing failures in the development of complex, large scale products and systems point towards weaknesses in the existing approaches. We argue that product development organizations are hindered by the many uncertainties that are inherent in the process. Common management heuristics ignore uncertainty and thus overly simplify the decision making process. Creating transparency regarding uncertainties and the associated risks (i.e. effect of uncertainties on design objectives) is not seen as an explicit priority. Consequently organizations are unable to balance risk and return in their development choices. Product development processes do not emphasize reduction of risks, particularly those risks that are apparent early in the process. In addition, the resilience of the PD system, i.e. its ability to deliver on-target results under uncertainty, is not deliberately designed to match the level of residual uncertainty. This chapter introduces the notion of Risk-Driven Design and its four principles of 1. Creating transparency regarding design risks; 2. Risk-driven decision making; 3. Minimizing uncertainty; and 4. Creating resilience.Massachusetts Institute of Technology. Lean Advancement InitiativeCenter for Clean Water and Clean Energy at MIT and KFUP

Predicting Clinical Outcome of Stroke Patients with Tractographic Feature

The volume of stroke lesion is the gold standard for predicting the clinical outcome of stroke patients. However, the presence of stroke lesion may cause neural disruptions to other brain regions, and these potentially damaged regions may affect the clinical outcome of stroke patients. In this paper, we introduce the tractographic feature to capture these potentially damaged regions and predict the modified Rankin Scale (mRS), which is a widely used outcome measure in stroke clinical trials. The tractographic feature is built from the stroke lesion and average connectome information from a group of normal subjects. The tractographic feature takes into account different functional regions that may be affected by the stroke, thus complementing the commonly used stroke volume features. The proposed tractographic feature is tested on a public stroke benchmark Ischemic Stroke Lesion Segmentation 2017 and achieves higher accuracy than the stroke volume and the state-of-the-art feature on predicting the mRS grades of stroke patients. In addition, the tractographic feature also yields a lower average absolute error than the commonly used stroke volume feature.Comment: 12 pages, 4 figures, 3 tables. Accepted by MICCAI-BrainLesion 2019 as an oral presentatio

Children's acceptance of milk with xylitol or sorbitol for dental caries prevention

BACKGROUND: Xylitol, a polyol sugar, has been shown to reduce dental caries when mixed with food or chewing gum. This study examines the taste acceptability of xylitol in milk as a first step toward measuring the effectiveness of xylitol in milk for the reduction of dental caries in a public health program. METHODS: Three different types of milk (Ultra High Temperature (UHT), powder and evaporated) were tested for acceptability by 75 Peruvian children (25 per milk group, ages 4 to 7 years). Each group evaluated xylitol and sorbitol in one type of milk. In the first phase, each child was presented with a tray of four plastic cups containing 50 ml of milk with 0.021 g/ml xylitol, 0.042 g/ml xylitol, 0.042 g/ml sorbitol or no sugar. Each child was asked to taste the samples in a self-selected order. After tasting each sample, the child placed the milk cup in front of one of three cartoon faces (smile, frown or neutral) representing the child's response to the taste of each sample. In the second phase, the child was asked to rank order the milk samples within each category (smile, frown or neutral). Ranks within categories were then combined to obtain a rank ordering for all the test samples. RESULTS: The ranking from best to worst for the samples across categories (UHT, powder, evaporated) was xylitol (0.0.042 g/ml), sorbitol (0.042 g/ml), xylitol (0.021 g/ml) and milk alone (Friedman's ANOVA). Xylitol and sorbitol were preferred over milk alone, and xylitol (0.042 g/ml) was preferred to sorbitol (0.042 g/ml)(p < .05 sign test). CONCLUSION: Milk sweetened with xylitol is well accepted by Peruvian children ages 4–7 years

Chemotherapy-induced nausea and vomiting in daily clinical practice: a community hospital-based study

Background Chemotherapy-induced nausea and vomiting (CINV) are major adverse effects of cancer chemotherapy. This study investigated: (1) the impact of CINV on patients' health-related quality of life (HRQL) in daily clinical practice; (2) the association between patient characteristics and type of antiemetics and CINV; and (3) the role of CINV in physicians' decisions to modify antiemetic treatment. Patients and methods This prospective, multicenter study was conducted in nine general hospitals in the Netherlands. During three consecutive chemotherapy cycles, patients used a diary to record episodes of nausea, vomiting and antiemetic use. For each cycle, these ratings were made 1 day prior to and 7 days after having received chemotherapy. The influence of CINV on patients' HRQL was evaluated with the Functional Living Index-Emesis (FLIE) questionnaire at day 6 of each treatment cycle. (Changes in) antiemetic use were recorded by the treating nurse. Patient inclusion took place between May 2005 and May 2007. Results Two hundred seventy-seven patients were enrolled in the study. Acute and delayed nausea during the first treatment cycle was reported by 39% and 68% of the patients, respectively. The comparable figures for acute and delayed vomiting were 12% and 23%. During the first and subsequent treatment cycle, approximately one-third of the patients indicated that CINV had a substantial impact on their daily lives. Female patients and younger patients reported significantly more CINV than male and older patients. At all treatment cycles, patients receiving treatment with moderately emetogenic chemotherapy, containing anthracycline, reported more acute nausea than patients receiving highly emetogenic chemotherapy. Acute vomiting was associated significantly with change in (i.e., additional) antiemetic treatment. Delayed CINV did not influence antiemetic treatment. Conclusion CINV continues to be a problem that adversely affects the daily lives of patients. CINV is worse in women and in younger patients. In daily clinical practice, acute CINV, but not delayed CINV, results in changes in antiemetic treatment. In view of the effects of not only acute, but also delayed CINV on daily life, more attention should be paid to adjustment of antiemetic treatment to cover CINV complaints, later during the chemotherapy cycle

Human Cord Blood Stem Cell-Modulated Regulatory T Lymphocytes Reverse the Autoimmune-Caused Type 1 Diabetes in Nonobese Diabetic (NOD) Mice

Background: The deficit of pancreatic islet b cells caused by autoimmune destruction is a crucial issue in type 1 diabetes (T1D). It is essential to fundamentally control the autoimmunity for treatment of T1D. Regulatory T cells (Tregs) play a pivotal role in maintaining self-tolerance through their inhibitory impact on autoreactive effector T cells. An abnormality of Tregs is associated with initiation of progression of T1D. Methodology/Principal Findings: Here, we report that treatment of established autoimmune-caused diabetes in NOD mice with purified autologous CD4 + CD62L + Tregs co-cultured with human cord blood stem cells (CB-SC) can eliminate hyperglycemia, promote islet b-cell regeneration to increase b-cell mass and insulin production, and reconstitute islet architecture. Correspondingly, treatment with CB-SC-modulated CD4 + CD62L + Tregs (mCD4CD62L Tregs) resulted in a marked reduction of insulitis, restored Th1/Th2 cytokine balance in blood, and induced apoptosis of infiltrated leukocytes in pancreatic islets. Conclusions/Significance: These data demonstrate that treatment with mCD4CD62L Tregs can reverse overt diabetes

Stochastic and epistemic uncertainty propagation in LCA

Purpose: When performing uncertainty propagation, most LCA practitioners choose to represent uncertainties by single probability distributions and to propagate them using stochastic methods. However the selection of single probability distributions appears often arbitrary when faced with scarce information or expert judgement (epistemic uncertainty). Possibility theory has been developed over the last decades to address this problem. The objective of this study is to present a methodology that combines probability and possibility theories to represent stochastic and epistemic uncertainties in a consistent manner and apply it to LCA. A case study is used to show the uncertainty propagation performed with the proposed method and compare it to propagation performed using probability and possibility theories alone. Methods: Basic knowledge on the probability theory is first recalled, followed by a detailed description of hal-00811827, version 1- 11 Apr 2013 epistemic uncertainty representation using fuzzy intervals. The propagation methods used are the Monte Carlo analysis for probability distribution and an optimisation on alpha-cuts for fuzzy intervals. The proposed method (noted IRS) generalizes the process of random sampling to probability distributions as well as fuzzy intervals, thus making the simultaneous use of both representations possible

Real-Time Epidemic Monitoring and Forecasting of H1N1-2009 Using Influenza-Like Illness from General Practice and Family Doctor Clinics in Singapore

10.1371/journal.pone.0010036PLoS ONE54

Anti-emetic drugs in oncology: pharmacology and individualization by pharmacogenetics

Objective Nausea and vomiting are the most distressful side effects of cytotoxic drugs in cancer patients. Antiemetics are commonly used to reduce these side effects. However, the current antiemetic efficacy is about 70–80% in patients treated with highly-emetogenic cytotoxic drugs. One of the potential factors explaining this suboptimal response is variability in genes encoding enzymes and proteins which play a role in metabolism, transport and receptors related to antiemetic drugs. Aim of this review was to describe the pharmacology and pharmacogenetic concepts of of antiemetics in oncology. Method Pharmacogenetic and pharmacology studies of antiemetics in oncology published between January 1997 and February 2010 were searched in PubMed. Furthermore, related textbooks were also used for exploring the pharmacology of antiemetic drugs. The antiemetic drugs which were searched were the 5-hydroxytryptamine 3 receptor antagonists (5-HT3RAs), dopamine antagonists, corticosteroids, benzodiazepines, cannabinoids, antihistamines and neurokinin-1 antagonists. Result The 5-HT3RAs are widely used in highly emetogenic chemotherapy in combination with dexamethasone and a neurokinin-1 antagonist, especially in acute phase. However, the dopamine antagonists and benzodiazepines were found more appropriate for use in breakthrough and anticipatory symptoms or in preventing the delayed phase of chemotherapy induced nausea and vomiting. The use of cannabinoids and antihistamines need further investigation. Only six articles on pharmacogenetics of the 5-HT3RAs in highly emetogenic chemotherapy are published. Specifically, these studies investigated the association of the efficacy of 5-HT3RAs and variants in the multi drug resistance 1 (MDR1) gene, 5-HT3A,B and C receptor genes and CYP2D6 gene. The pharmacogenetic studies of the other antiemetics were not found in this review. Conclusion It is concluded that pharmacogenetic studies with antiemetics are sparse. It is too early to implement results of pharmacogenetic association studies of antiemetic drugs in clinical practice: confirmation of early findings is required

Do People Taking Flu Vaccines Need Them the Most?

Background: A well targeted flu vaccine strategy can ensure that vaccines go to those who are at the highest risk of getting infected if unvaccinated. However, prior research has not explicitly examined the association between the risk of flu infection and vaccination rates. Purpose: This study examines the relationship between the risk of flu infection and the probability of getting vaccinated. Methods: Nationally representative data from the US and multivariate regression models were used to estimate what individual characteristics are associated with (1) the risk of flu infection when unvaccinated and (2) flu vaccination rates. These results were used to estimate the correlation between the probability of infection and the probability of getting vaccinated. Separate analyses were performed for the general population and the high priority population that is at increased risk of flu related complications. Results: We find that the high priority population was more likely to get vaccinated compared to the general population. However, within both the high priority and general populations the risk of flu infection when unvaccinated was negatively correlated with vaccination rates (r = 20.067, p,0.01). This negative association between the risk of infection when unvaccinated and the probability of vaccination was stronger for the high priority population (r = 20.361, p,0.01). Conclusions: There is a poor match between those who get flu vaccines and those who have a high risk of flu infectio

Fortune Favours the Bold: An Agent-Based Model Reveals Adaptive Advantages of Overconfidence in War

Overconfidence has long been considered a cause of war. Like other decision-making biases, overconfidence seems detrimental because it increases the frequency and costs of fighting. However, evolutionary biologists have proposed that overconfidence may also confer adaptive advantages: increasing ambition, resolve, persistence, bluffing opponents, and winning net payoffs from risky opportunities despite occasional failures. We report the results of an agent-based model of inter-state conflict, which allows us to evaluate the performance of different strategies in competition with each other. Counter-intuitively, we find that overconfident states predominate in the population at the expense of unbiased or underconfident states. Overconfident states win because: (1) they are more likely to accumulate resources from frequent attempts at conquest; (2) they are more likely to gang up on weak states, forcing victims to split their defences; and (3) when the decision threshold for attacking requires an overwhelming asymmetry of power, unbiased and underconfident states shirk many conflicts they are actually likely to win. These “adaptive advantages” of overconfidence may, via selection effects, learning, or evolved psychology, have spread and become entrenched among modern states, organizations and decision-makers. This would help to explain the frequent association of overconfidence and war, even if it no longer brings benefits today