Managing the trade-off implications of global supply

The cost versus response trade-off is a growing logistics issue due to many markets being increasingly characterized by demand uncertainty and shorter product life cycles. This is exacerbated further with supply increasingly moving to low cost global sources. However, the poor response implications of global supply are often not addressed or even acknowledged when undertaking such decisions. Consequently, various practical approaches to minimising, postponing or otherwise managing the impact of the demand uncertainty are often only adopted retrospectively. Even though such generic solutions are documented through case examples we lack effective tools and concepts to support the proactive identification and resolution of such trade-offs. This paper reports on case-based theory building research, involving three cases from the UK and USA used in developing a conceptual model with associated tools, in support of such a process

Deriving a mutation index of carcinogenicity using protein structure and protein interfaces

With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr.ac.uk/

The effect of a complementary e-learning course on implementation of a quality improvement project regarding care for elderly patients: a stepped wedge trial

<p>Abstract</p> <p>Background</p> <p>Delirium occurs frequently in elderly hospitalised patients and is associated with higher mortality, increased length of hospital stay, functional decline, and admission to long-term care. Healthcare professionals frequently do not recognise delirium, indicating that education can play an important role in improving delirium care for hospitalised elderly. Previous studies have indicated that e-learning can provide an effective way of educating healthcare professionals and improving quality of care, though results are inconsistent.</p> <p>Methods and design</p> <p>This stepped wedge cluster randomised trial will assess the effects of a complementary delirium e-learning course on the implementation of quality improvement initiative, which aims to enhance the recognition and management of delirium in elderly patients. The trial will be conducted in 18 Dutch hospitals and last 11 months. Measurements will be taken in all participating wards using monthly record reviews, in order to monitor delivered care. These measurements will include the percentage of elderly patients who were screened for the risk of developing delirium, use of the Delirium Observation Screening scale, use of nursing or medical interventions, and the percentage of elderly patients who were diagnosed with delirium. Data regarding the e-learning course will be gathered as well. These data will include user characteristics, information regarding use of the course, delirium knowledge before and after using the course, and the attitude and intentions of nurses concerning delirium care.</p> <p>Setting</p> <p>The study will be conducted in internal medicine and surgical wards of eighteen hospitals that are at the beginning stages of implementing the Frail Elderly Project in the Netherlands.</p> <p>Discussion</p> <p>Better recognition of elderly patients at risk for delirium and subsequent care is expected from the introduction of an e-learning course for nurses that is complementary to an existing quality improvement project. This trial has the potential to demonstrate that e-learning can be a vital part of the implementation process, especially for quality improvement projects aimed at complex health issues such as delirium. The study will contribute to a growing body of knowledge concerning e-learning and the effects it can have on knowledge as well as delivered care.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2885">NTR2885</a></p

A systematic review of dietary, nutritional, and physical activity interventions for the prevention of prostate cancer progression and mortality

PURPOSE: Given the long-term, although potentially fatal, nature of prostate cancer, there is increasing observational evidence for the reduction in disease progression and mortality through changes in lifestyle factors. METHODS: We systematically reviewed dietary, nutritional, and physical activity randomized interventions aimed at modifying prostate cancer progression and disease-specific mortality, including a detailed assessment of risk of bias and methodological quality. RESULTS: Forty-four randomized controlled trials of lifestyle interventions, with prostate cancer progression or mortality outcomes, were identified. Substantial heterogeneity of the data prevented a meta-analysis. The included trials involved 3,418 prostate cancer patients, median 64 men per trial, from 13 countries. A trial of a nutritional supplement of pomegranate seed, green tea, broccoli, and turmeric; a trial comparing flaxseed, low-fat diet, flaxseed, and low-fat diet versus usual diet; and a trial supplementing soy, lycopene, selenium, and coenzyme Q10, all demonstrated beneficial effects. These trials were also assessed as having low risk of bias and high methodological quality (as were seven other trials with no evidence of benefit). The remaining trials were either underpowered, at high or unclear risk of bias, inadequately reported, of short duration or measured surrogate outcomes of unproven relationship to mortality or disease progression, which precluded any benefits reported being reliable. CONCLUSION: Large, well-designed randomized trials with clinical endpoints are recommended for lifestyle modification interventions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10552-015-0659-4) contains supplementary material, which is available to authorized users

Targeting cancer metabolism: a therapeutic window opens

Genetic events in cancer activate signalling pathways that alter cell metabolism. Clinical evidence has linked cell metabolism with cancer outcomes. Together, these observations have raised interest in targeting metabolic enzymes for cancer therapy, but they have also raised concerns that these therapies would have unacceptable effects on normal cells. However, some of the first cancer therapies that were developed target the specific metabolic needs of cancer cells and remain effective agents in the clinic today. Research into how changes in cell metabolism promote tumour growth has accelerated in recent years. This has refocused efforts to target metabolic dependencies of cancer cells as a selective anticancer strategy.Burroughs Wellcome FundSmith Family FoundationStarr Cancer ConsortiumDamon Runyon Cancer Research FoundationNational Institutes of Health (U.S.

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

Empathy among undergraduate medical students: A multi-centre cross-sectional comparison of students beginning and approaching the end of their course

BACKGROUND: Although a core element in patient care the trajectory of empathy during undergraduate medical education remains unclear. Empathy is generally regarded as comprising an affective capacity: the ability to be sensitive to and concerned for, another and a cognitive capacity: the ability to understand and appreciate the other person's perspective. The authors investigated whether final year undergraduate students recorded lower levels of empathy than their first year counterparts, and whether male and female students differed in this respect. METHODS: Between September 2013 and June 2014 an online questionnaire survey was administered to 15 UK, and 2 international medical schools. Participating schools provided both 5-6 year standard courses and 4 year accelerated graduate entry courses. The survey incorporated the Jefferson Scale of Empathy-Student Version (JSE-S) and Davis's Interpersonal Reactivity Index (IRI), both widely used to measure medical student empathy. Participation was voluntary. Chi squared tests were used to test for differences in biographical characteristics of student groups. Multiple linear regression analyses, in which predictor variables were year of course (first/final); sex; type of course and broad socio-economic group were used to compare empathy scores. RESULTS: Five medical schools (4 in the UK, 1 in New Zealand) achieved average response rates of 55 % (n = 652) among students starting their course and 48 % (n = 487) among final year students. These schools formed the High Response Rate Group. The remaining 12 medical schools recorded lower response rates of 24.0 % and 15.2 % among first and final year students respectively. These schools formed the Lower Response Rate Group. For both male and female students in both groups of schools no significant differences in any empathy scores were found between students starting and approaching the end of their course. Gender was found to significantly predict empathy scores, with females scoring higher than males. CONCLUSIONS: Participant male and female medical students approaching the end of their undergraduate education, did not record lower levels of empathy, compared to those at the beginning of their course. Questions remain concerning the trajectory of empathy after qualification and how best to support it through the pressures of starting out in medical practice

The landscape of somatic copy-number alteration across human cancers

available in PMC 2010 August 18.A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-κΒ pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types.National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, P50CA90578)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, R01CA109038))National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, R01CA109467)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, P01CA085859)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, P01CA 098101)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, K08CA122833