Design x Science cards

A deck of cards to support collaborative ideation in multidisciplinary Design and Science projects

The role of illness acuity on the association between frailty and mortality in emergency department patients referred to internal medicine.

Background: we investigated whether two frailty tools predicted mortality among emergency department (ED) patients referred to internal medicine and how the level of illness acuity influenced any association between frailty and mortality.Methods: two tools, embedded in a Comprehensive Geriatric Assessment (CGA), were the clinical frailty scale (CFS) and a 57-item deficit accumulation frailty index (FI-CGA). Illness acuity was assessed using the Canadian Triage and Acuity Scale (CTAS). We examined all-cause 30-day and 6-month mortality and time to death.Results: in 808 ED patients (mean age ± SD 80.8 ± 8.8, 54.4% female), the mean FI-CGA score was 0.44 ± 0.14, and the CFS was 5.6 ± 1.6. A minority (307; 38%) were classified as having high acuity (CTAS: 1-2). The 30-day mortality rate was 17%; this increased to 34% at 6 months. Compared to well patients with low acuity, the risk of 30-day mortality was 22.5 times (95% CI: 9.35-62.12) higher for severely frail patients with high acuity; 53% of people with very severe frailty (CFS = 8) and high acuity died within 30 days. When acuity was low, the risk for 30-day mortality was significantly higher only among those with very high levels of frailty (CFS 7-9, FI-CGA > 0.5). When acuity was high, even lower levels of frailty (CFS 5-6, FI-CGA 0.4-0.5) were associated with higher 30-day mortality.Conclusions: across levels of frailty, higher acuity increased mortality risk. When acuity was low, the risk was significant only when the degree of frailty was high, whereas when acuity was high, even lower levels of frailty were associated with greater mortality risk

Total cost of ownership in the services sector: A case study

Few detailed studies exist of the trade-offs to be made when developing a comprehensive, strategically focused total cost of ownership (TCO) model. Moreover, most studies of TCO have been conducted in manufacturing firms, with little or no TCO research directed toward service organizations. This research presents the results of a study conducted at a leading vehicle glass repair and replacement organization. The results show how TCO information can be used for strategic decision making regarding the allocation of volumes. This information can also be used in the identification of improvement areas for preferred suppliers by introducing a limited number of key performance indicators that have a significant impact on the TCO of supplier offerings. The paper highlights some of the trade-offs required in designing such a model. It fills an existing literature gap that allows service organizations to better understand the development and implementation of total cost measurement systems. Copyrigh

Energy coupling of membrane transport and efficiency of sucrose dissimilation in yeast

Proton coupled transport of α-glucosides via Mal11 into Saccharomyces cerevisiae costs one ATP per imported molecule. Targeted mutation of all three acidic residues in the active site resulted in sugar uniport, but expression of these mutant transporters in yeast did not enable growth on sucrose. We then isolated six unique transporter variants of these mutants by directed evolution of yeast for growth on sucrose. In three variants, new acidic residues emerged near the active site that restored proton-coupled sucrose transport, whereas the other evolved transporters still catalysed sucrose uniport. The localization of mutations and transport properties of the mutants enabled us to propose a mechanistic model of proton-coupled sugar transport by Mal11. Cultivation of yeast strains expressing one of the sucrose uniporters in anaerobic, sucrose-limited chemostat cultures indicated an increase in the efficiency of sucrose dissimilation by 21% when additional changes in strain physiology were taken into account. We thus show that a combination of directed and evolutionary engineering results in more energy efficient sucrose transport, as a starting point to engineer yeast strains with increased yields for industrially relevant products

Characterization of immune response to neurofilament light in experimental autoimmune encephalomyelitis

PMCID: PMC3856490This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.PMCID: PMC385649

Adaptive Tracking of Angular Velocity for a Planar Rigid Body With Unknown Models for Inertia and Input Nonlinearity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57795/1/AdaptiveTrackingTACTTCST1D.pd

p53 and P-glycoprotein are often co-expressed and are associated with poor prognosis in breast cancer.

Expression of both P-glycoprotein (P-gp) and mutant p53 have recently been reported to be associated with poor prognosis of breast cancer. The expression of P-gp is associated in vitro and in vivo with cross-resistance to several anti-cancer drugs. p53 plays a regulatory role in apoptosis, and mutant p53 has been suggested to be involved in drug resistance. Interestingly, in vitro experiments have shown that mutant p53 can activate the promoter of the MDR1 gene, which encodes P-gp. We investigated whether p53 and P-gp are simultaneously expressed in primary breast cancer cells and analysed the impact of the co-expression on patients prognosis. Immunohistochemistry was used to investigate P-gp expression (JSB-1, C219) and nuclear p53 accumulation (DO-7) in 20 operable chemotherapy untreated and 30 locally advanced breast cancers undergoing neoadjuvant chemotherapy with doxorubicin and cyclophosphamide. Double immunostaining showed that P-gp expression and nuclear p53 accumulation often occur concomitantly in the same tumour cells. A correlation between p53 and P-gp expression was found in all 50 breast cancers (P = 0.003; Fisher's exact test). P-gp expression, nuclear p53 accumulation, and co-expression of p53 and P-gp were more frequently observed in locally advanced breast cancers than in operable breast cancers (P = 0.0004, P = 0.048; P = 0.002 respectively. Fisher's exact test). Co-expression of p53 and P-gp was the strongest prognostic factor for shorter survival by multivariate analysis (P = 0.004) in the group of locally advanced breast cancers (univariate analysis: P = 0.0007). Only 3 out of 13 samples sequentially taken before and after chemotherapy displayed a change in P-gp or p53 staining. In conclusion, nuclear p53 accumulation is often associated with P-gp expression in primary breast cancer, and simultaneous expression of p53 and P-gp is associated with shorter survival in locally advanced breast cancer patients. Co-expression of P-gp and mutant p53 belong to a series of molecular events resulting in a more aggressive phenotype, drug resistance and poor prognosis