Data-driven through-life costing to support product lifecycle management solutions in innovative product development

Innovative product usually refers to product that comprises of creativity and new ideas. In the development of such a new product, there is often a lack of historical knowledge and data available to be used to perform cost estimation accurately. This is due to the fact that traditional cost estimation methods are used to predict costs only after a product model has been built, and not at an early design stage when there is little data and information available. In light of this, original equipment manufacturers are also facing critical challenges of becoming globally competitive and increasing demands from customer for continuous innovation. To alleviate these situations this research has identified a new approach to cost modelling with the inclusion of product lifecycle management solutions to address innovative product development.The aim of this paper, therefore, is to discuss methods of developing an extended-enterprise data-driven through-life cost estimating method for innovative product development

Brief inactivation of c-Myc is not sufficient for sustained regression of c-Myc-induced tumours of pancreatic islets and skin epidermis

Background Tumour regression observed in many conditional mouse models following oncogene inactivation provides the impetus to develop, and a platform to preclinically evaluate, novel therapeutics to inactivate specific oncogenes. Inactivating single oncogenes, such as c-Myc, can reverse even advanced tumours. Intriguingly, transient c-Myc inactivation proved sufficient for sustained osteosarcoma regression; the resulting osteocyte differentiation potentially explaining loss of c-Myc's oncogenic properties. But would this apply to other tumours? Results We show that brief inactivation of c-Myc does not sustain tumour regression in two distinct tissue types; tumour cells in pancreatic islets and skin epidermis continue to avoid apoptosis after c-Myc reactivation, by virtue of Bcl-xL over-expression or a favourable microenvironment, respectively. Moreover, tumours progress despite reacquiring a differentiated phenotype and partial loss of vasculature during c-Myc inactivation. Interestingly, reactivating c-Myc in β-cell tumours appears to result not only in further growth of the tumour, but also re-expansion of the accompanying angiogenesis and more pronounced β-cell invasion (adenocarcinoma). Conclusions Given that transient c-Myc inactivation could under some circumstances produce sustained tumour regression, the possible application of this potentially less toxic strategy in treating other tumours has been suggested. We show that brief inactivation of c-Myc fails to sustain tumour regression in two distinct models of tumourigenesis: pancreatic islets and skin epidermis. These findings challenge the potential for cancer therapies aimed at transient oncogene inactivation, at least under those circumstances where tumour cell differentiation and alteration of epigenetic context fail to reinstate apoptosis. Together, these results suggest that treatment schedules will need to be informed by knowledge of the molecular basis and environmental context of any given cancer

The “Journey” of Doctoral Study in Applied Psychology: Lived Experiences of Students in Counseling, Clinical, and School Psychology

A qualitative methodology was adopted to explore the lived experiences of doctoral level students in applied psychology. A total of 15 students ranging in age from 24 to 43, who were at varying levels of their doctoral education, participated in individual semi-structured interviews exploring themes related to influences for the pursuit of graduate study, experiences in their program of study, and general reflections of the graduate school journey. All interviews were conducted from a constructivist-interpretivist model, transcribed verbatim, and analyzed using a phenomenological coding approach (Creswell, 2012; Moustakas, 1994). Emergent broad themes included antecedents leading to graduate study, current experience of doctoral education, and reflections on the doctoral experience. Implications for future research are discussed and recommendations for graduate programs based on findings are provided

Myocardin overexpression is sufficient for promoting the development of a mature smooth muscle cell-like phenotype from human embryonic stem cells.

BACKGROUND: Myocardin is thought to have a key role in smooth muscle cell (SMC) development by acting on CArG-dependent genes. However, it is unclear whether myocardin-induced SMC maturation and increases in agonist-induced calcium signalling are also associated with increases in the expression of non-CArG-dependent SMC-specific genes. Moreover, it is unknown whether myocardin promotes SMC development from human embryonic stem cells. METHODOLOGY/PRINCIPAL: Findings The effects of adenoviral-mediated myocardin overexpression on SMC development in human ESC-derived embryoid bodies were investigated using immunofluorescence, flow cytometry and real time RT-PCR. Myocardin overexpression from day 10 to day 28 of embryoid body differentiation increased the number of smooth muscle α-actin(+) and smooth muscle myosin heavy chain(+) SMC-like cells and increased carbachol-induced contractile function. However, myocardin was found to selectively regulate only CArG-dependent SMC-specific genes. Nevertheless, myocardin expression appeared to be sufficient to specify the SMC lineage. CONCLUSIONS/SIGNIFICANCE: Myocardin increases the development and maturation of SMC-like cells from human embryonic stem cells despite not activating the full repertoire of SMC genes. These findings have implications for vascular tissue engineering and other applications requiring large numbers of functional SMCs

Through life costing in defence electronic systems: an integrated data-driven multi-level approach

Cost estimating is a business process that is critical to the defence sector, where many products have low volumes and long life cycles. The nature of a defence system is often unique (for example, a naval platform) which consists of a number of sub-systems and components. For the design of such a system cost estimating is a critical task, in particular the requirement to predict the cost throughout the systems lifetime. The aim of this paper therefore is to discuss an integrated approach that provides a general framework for through life costing in defence systems via the development of: (1) a generic data library to support designers and cost estimators, (2) data searching and transfer mechanisms to support a top-down and bottom-up hybrid cost modelling approach, (3) capturing reliability data to support product services. The paper is divided into several sections, first, a review of relevant research projects concerning integration and data capture for cost modelling. This is followed by a section, which highlights problems of performing cost estimates for low volume products, and subsequently the proposed solution, methods of cost estimation and example applications. Perhaps most importantly, the methods created in this research are able to enhance decision-making and accelerate the responsiveness of the business bidding process

Data Modelling and Optimization in Cost Estimation for Innovative Low Volume Product Development

This paper reports on the progress of the research and development of a data modelling and optimization method to support cost estimation in the product development process. This paper forms part of an investigation into Through-Life Costing of innovative low volume long life defence electronic systems. The paper briefly covers the literature review in the area of cost estimation in product development, in particularly the data sets needed to perform cost estimation and the method of modelling the data and the optimization techniques. The propose approach will be used to support cost estimation in product development decisions of innovative low volume product development

A three-year multifaceted intervention to prevent obesity in children of Mexican-heritage.

BackgroundObesity and overweight have increased dramatically in the United States over the last decades. The complexity of interrelated causal factors that result in obesity needs to be addressed within the cultural dynamic of sub-populations. In this study, we sought to estimate the effects of a multifaceted, community-based intervention on body mass index (BMI) among Mexican-heritage children.MethodsNiños Sanos, Familia Sana (Healthy Children, Healthy Family) was a quasi-experimental intervention study designed to reduce the rate of BMI growth among Mexican-heritage children in California's Central Valley. Two rural communities were matched based on demographic and environmental characteristics and were assigned as the intervention or comparison community. The three-year intervention included parent workshops on nutrition and physical activity; school-based nutrition lessons and enhanced physical education program for children; and a monthly voucher for fruits and vegetables. Eligible children were between 3 and 8 years old at baseline. Intent-to-treat analyses were estimated using linear mixed-effect models with random intercepts. We ran a series of models for each gender where predictors were fixed except interactions between age groups and obesity status at baseline with intervention to determine the magnitude of impact on BMI.ResultsAt baseline, mean (SD) BMI z-score (zBMI) was 0.97 (0.98) in the intervention group (n = 387) and 0.98 (1.02) in the comparison group (n = 313) (NS). The intervention was significantly associated with log-transformed BMI (β = 0.04 (0.02), P = 0.03) and zBMI (β = 0.25 (0.12), P = 0.04) among boys and log-transformed BMI among obese girls (β = - 0.04 (0.02), P = 0.04). The intervention was significantly and inversely associated with BMI in obese boys and girls across all age groups and normal weight boys in the oldest group (over 6 years) relative to their counterparts in the comparison community.ConclusionsA community-based, multifaceted intervention was effective at slowing the rate of BMI growth among Mexican-heritage children. Our findings suggest that practitioners should consider strategies that address gender disparities and work with a variety of stakeholders to target childhood obesity.Trial registrationclinicaltrials.gov Identifier: NCT01900613 . Registered 16th July 2013

Cloned defective interfering influenza virus protects ferrets from pandemic 2009 influenza A virus and allows protective immunity to be established

Influenza A viruses are a major cause of morbidity and mortality in the human population, causing epidemics in the winter, and occasional worldwide pandemics. In addition there are periodic outbreaks in domestic poultry, horses, pigs, dogs, and cats. Infections of domestic birds can be fatal for the birds and their human contacts. Control in man operates through vaccines and antivirals, but both have their limitations. In the search for an alternative treatment we have focussed on defective interfering (DI) influenza A virus. Such a DI virus is superficially indistinguishable from a normal virus but has a large deletion in one of the eight RNAs that make up the viral genome. Antiviral activity resides in the deleted RNA. We have cloned one such highly active DI RNA derived from segment 1 (244 DI virus) and shown earlier that intranasal administration protects mice from lethal disease caused by a number of different influenza A viruses. A more cogent model of human influenza is the ferret. Here we found that intranasal treatment with a single dose of 2 or 0.2 µg 244 RNA delivered as A/PR/8/34 virus particles protected ferrets from disease caused by pandemic virus A/California/04/09 (A/Cal; H1N1). Specifically, 244 DI virus significantly reduced fever, weight loss, respiratory symptoms, and infectious load. 244 DI RNA, the active principle, was amplified in nasal washes following infection with A/Cal, consistent with its amelioration of clinical disease. Animals that were treated with 244 DI RNA cleared infectious and DI viruses without delay. Despite the attenuation of infection and disease by DI virus, ferrets formed high levels of A/Cal-specific serum haemagglutination-inhibiting antibodies and were solidly immune to rechallenge with A/Cal. Together with earlier data from mouse studies, we conclude that 244 DI virus is a highly effective antiviral with activity potentially against all influenza A subtypes

Chronic Hepatitis B Prevalence Among Foreign‐Born and U.S.‐Born Adults in the United States, 1999‐2016

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154388/1/hep30831-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154388/2/hep30831.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154388/3/hep30831_am.pd