The selection of subcontractors: is price the major factor?

The philosophy of ‘lowest price wins’ in the selection of subcontractors often leads to problems with quality of work and claims for further costs. Since Latham (1994), many models have offered selection methods that take account of a wide range of quality criteria as well as price. A review of existing literature and models enables a list of selection criteria to be drawn up and a survey ascertains which selection criteria are considered most important and whether opinions change when faced with different types of project. The results of the questionnaire are analysed through the use of Simple Relative Indexes, Spearman’s Rank Correlation Coefficient tests and a number of T-tests. It is established that price is no longer considered the only important factor in subcontractor selection, and that health and safety, past performance, and insurance cover are considered equally important and, in some scenarios, more important than price

The Benedum Collaborative Model of Teacher Education Student Handbook

The College of Human Resources & Education welcomes you as students in the Five-Year Teacher Education Program. You will find that your experiences in the Benedum Collaborative will prepare you well as you begin your work in the teaching profession. Our partnership with the professional development schools in the Collaborative provides the setting for clinical experiences that build on your course work at West Virginia University

The Metaphors of Emerging Technologies: Unpacking the disconnects between the "what" and the "how" in the world of "online shopping"

Conference paper preprint, 9th International Conference on Technology Policy and Innovation, Santorini, GreeceEmerging technologies often produce unexpected consequences that existing institutions and policies are unable to deal with effectively. Because predicting the consequences of technological change is difficult, responses to emerging technologies tend to be reactive (if not passive), rather than proactive. Improved understanding of the potential consequences of a particular technology would enable policymakers and analysts to implement appropriate measures more quickly and perhaps even act prospectively. This paper proposes a general approach that can be used to identify potential sources of disruption resulting from emerging technologies in order to enable proactive policy actions to limit the negative consequences of these disruptions. New technologies are often characterized through the use of metaphors and/or comparisons to existing technologies. While such comparisons provide an easy way to generate understanding of a new technology they often also neglect important aspects of that technology. As a result, the use of metaphors and comparisons creates a disconnect between what the metaphor suggests is happening and what is actually taking place. The incompleteness of the metaphors leads to a disparity in the appreciation of the benefits, and pitfalls of a new technology. This disparity allows certain aspects of the technology to be ignored and/or exploited, with potentially disruptive social consequences. An analysis of the mismatch between metaphorical characterizations and the actual attributes of a new technology can help identify otherwise overlooked issues and determine if existing institutions and policies can adequately respond. This paper uses a study of personalization technologies by online retailers to demonstrate the potential for disruption caused by failures of metaphor to adequately describe new technologies. Online retailing technologies have equipped firms with tools that allow them to move closer to the ``mass market of one" --- satisfying the demands of a mass market through individually-targeted sales strategies (i.e., personalization). While the metaphors of ``shopping" and ``catalog" have been used to describe online retail ``stores," these metaphors fail to capture several key aspects of online retail technologies such as aggregation, replication, persistence, and analysis of the personal data easily collected by such businesses. As a result, the institutions that exist to protect consumers when dealing with traditional, physical stores may no longer be sufficient. Furthermore, the pervasiveness of the metaphor undermines the ability of consumers to understand or debate the negative consequences of personalization, especially in the areas of privacy and identity.National Science Foundation, IGERT Progra

The effects of continual consumption of origanum vulgare on liver transcriptomics

Pathogen control is re-emerging as a significant challenge to the health of both humans and animals. The livestock industry is in the process of massively replacing in-feed antibiotics with organic production friendly plant-based products. Nutrigenomics as a science of the effects of food constituents on gene expression is shedding more light on both benefits and detrimental side-effects of feed additive prolonged consumption on the host, indicating the need to understand the feed– host interactions and their influence on the host disease profile. In this study, we investigated the effects of 2% oregano powder supplementation on the liver gene expression in healthy male broilers from the hatch to 6 weeks of age. Deep RNAseq was performed on average 113.3 million paired and quality trimmed sequences per sample and four samples for the control and treatment each. The results demonstrate the severity of oregano effect on liver gene expression with substantial modifications in steroid hormone regulation, fat and carbohydrate metabolism alterations and strong influence on the host disease and function profile. Oregano supplementation was able to interfere with the transcriptional effects of a range of registered drugs and to significantly transcriptionally inhibit a range of cancer disease categories including liver cancer, and to modify fat and carbohydrate metabolism

Inclusion of mobile phone numbers into an ongoing population health survey in Australia using an overlapping dual frame: description of methods, call outcomes and acceptance by staff and respondents

In Australia telephone surveys has been the method of choice for ongoing population health surveys. Although it was estimated in 2011 that 20% of the population were mobile phone only persons the inclusion of mobile only phone users into these existing landline population health surveys has not occurred. This paper is part of a project that is looking in detail at the inclusion of mobile phone numbers into an ongoing population health survey in Australia. This paper describes the methods used, the call outcomes and acceptance by the population, supervisors and interviewing staff

microRNA199a based post-transcriptional detargeting of gene vectors for Hepatocellular Carcinoma

A gene therapeutic platform needs to be both efficient and safe. The criterion of safety is particularly important for diseases like hepatocellular carcinoma (HCC), which develop in a background of an already compromised liver. Gene vectors can be constructed either by targeting HCC or by detargeting liver and/or other major organs. miRNA-based negative detargeting has gained considerable attention in recent times due to its effectiveness and the ease with which it can be adapted into current gene delivery vectors. In this study, we provide a proof-of-concept using miRNA199a as a negative targeting agent. We introduced vectors harboring reporters with miRNA199a binding sites in cells expressing high endogenous levels of miRNA199a and compared the reporter expression in HCC cells with low endogenous miRNA199a. We observed that the expression of reporters with miRNA199a binding sites is significantly inhibited in miRNA199a-positive cells, whereas minimal effect was observed in miRNA199a-negative HCC cells. In addition, we created a post-transcriptionally regulated suicide gene therapeutic system based on cytosine deaminase (CD)/5-fluorocytosine (5-FC) exploiting miRNA199a binding sites and observed significantly lower cell death for miRNA199a-positive cells. Furthermore, we observed a decrease in the levels of miRNA199 in 3D tumorspheres of miRNA199a-positive Hepa1-6 cells and a reduction in the inhibition of reporter expression after transfection in these 3D models when compared with 2D Hepa1-6 cells. In summary, we provide evidence of miRNA199a-based post-transcriptional detargeting with relevance to HCC gene therapy

miRNA122a regulation of gene therapy vectors targeting hepatocellular cancer stem cells

In this study, we report a miRNA122a based targeted gene therapy for hepatocellular cancer stem cells (CSCs). First, we assessed the levels of miRNA122a in normal human hepatocytes, a panel of hepatocellular carcinoma (HCC) cell lines and hepatocellular CSCs observing its significant downregulation in HCC and CSCs. The miRNA122a binding site was then incorporated at the 3'-UTR of reporter genes gaussia luciferase (GLuc) and eGFP which resulted in significant hepatocyte detargeting. Using this strategy for the delivery of gene directed enzyme prodrug therapy (GDEPT) utilizing the cytosine deaminase/5-fluorocytosine (CD/5-FC) system, we showed significant killing in cells with low or no miRNA122a while those cells, such as hepatocytes with high miRNA122a were largely spared. Next, we showed that CSC enriched tumorspheres exhibit a significant downregulation of miRNA122a expression providing a rational to exploit its binding site for targeted gene delivery. Using plasmids harboring reporters GLuc and eGFP with or without miR122a binding sites, we showed high reporter expression in the CSCs and little reported expression in the non-enriched cultures. Finally, we demonstrate the efficacy of miRNA122a based post-transcriptionally targeted GDEPT for hepatocellular CSCs

A systematic approach for the accurate non-invasive estimation of blood glucose utilizing a novel light-tissue interaction adaptive modelling scheme

Diabetes is one of the biggest health challenges of the 21st century. The obesity epidemic, sedentary lifestyles and an ageing population mean prevalence of the condition is currently doubling every generation. Diabetes is associated with serious chronic ill health, disability and premature mortality. Long-term complications including heart disease, stroke, blindness, kidney disease and amputations, make the greatest contribution to the costs of diabetes care. Many of these long-term effects could be avoided with earlier, more effective monitoring and treatment. Currently, blood glucose can only be monitored through the use of invasive techniques. To date there is no widely accepted and readily available non-invasive monitoring technique to measure blood glucose despite the many attempts. This paper challenges one of the most difficult non-invasive monitoring techniques, that of blood glucose, and proposes a new novel approach that will enable the accurate, and calibration free estimation of glucose concentration in blood. This approach is based on spectroscopic techniques and a new adaptive modelling scheme. The theoretical implementation and the effectiveness of the adaptive modelling scheme for this application has been described and a detailed mathematical evaluation has been employed to prove that such a scheme has the capability of extracting accurately the concentration of glucose from a complex biological media

Monitoring Immune Checkpoint Regulators as Predictive Biomarkers in Hepatocellular Carcinoma

The global burden of hepatocellular carcinoma (HCC), one of the frequent causes of cancer-related deaths worldwide, is rapidly increasing partly due to the limited treatment options available for this disease and recurrence due to therapy resistance. Immune checkpoint inhibitors that are proved to be beneficial in the treatment of advanced melanoma and other cancer types are currently in clinical trials in HCC. These ongoing trials are testing the efficacy and safety of a few select checkpoints in HCC. Similar to observations in other cancers, these immune checkpoint blockade treatments as monotherapy may benefit only a fraction of HCC patients. Studies that assess the prevalence and distribution of other immune checkpoints/modulatory molecules in HCC have been limited. Moreover, robust predictors to identify which HCC patients will respond to immunotherapy are currently lacking. The objective of this study is to perform a comprehensive evaluation on different immune modulators as predictive biomarkers to monitor HCC patients at high risk for poor prognosis. We screened publically available HCC patient databases for the expression of previously well described immune checkpoint regulators and evaluated the usefulness of these immune modulators to predict high risk, patient overall survival and recurrence. We also identified the immune modulators that synergized with known immune evasion molecules programmed death receptor ligand-1 (PD-L1), programmed cell death protein-1 (PD-1), and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and correlated with worse patient outcomes. We evaluated the association between the expression of epithelial-to-mesenchymal transition (EMT) markers and PD-L1 in HCC patient tumors. We also examined the relationship of tumor mutational burden with HCC patient survival. Notably, expression of immune modulators B7-H4, PD-L2, TIM-3, and VISTA were independently associated with worse prognosis, while B7-H4, CD73, and VISTA predicted low recurrence-free survival. Moreover, the prognosis of patients expressing high PD-L1 with high B7-H4, TIM-3, VISTA, CD73, and PD-L2 expression was significantly worse. Interestingly, PD-L1 expression in HCC patients in the high-risk group was closely associated with EMT marker expression and prognosticates poor survival. In HCC patients, high tumor mutational burden (TMB) predicted worse patient outcomes than those with low TMB

Population changes in a whale breeding ground revealed by citizen science noninvasive genetics

Historical exploitation, and a combination of current anthropogenic impacts, such as climate change and habitat degradation, impact the population dynamics of marine mammalian megafauna. Right whales (Eubalaena spp.) are large cetaceans recovering from hunting, whose reproductive and population growth rate appear to be impacted by climate change. We apply noninvasive genetic methods to monitor southern right whale (E. australis, SRW) and test the application of noninvasive genetics to minimise the observer effects on the population. Our aim is to describe population structure, and interdecadal and interannual changes to assess species status in the Great Acceleration period of Anthropocene. As a basis for population genetic analyses, we collected samples from sloughed skin during post-migration epidermal moult. Considering the exploration-exploitation dilemma, we collaborated with whale watching companies, as part of a citizen science approach and to reduce ad hoc logistic operations and biopsy equipment. We used mitochondrial and microsatellite data and population genetic tools. We report for the first time the genetic composition and differentiation of the Namibian portion of the range. Population genetic parameters suggest that South Africa hosts the largest population. This corresponds with higher estimates of current gene flow from Africa compared to older samples. We have observed considerable interannual variation in population density at the breeding ground and an interdecadal shift in genetic variability, evidenced by an increase in the point estimate inbreeding. Clustering analyses confirmed differentiation between the Atlantic and Indo-Pacific, presumably originating during the ice ages. We show that population monitoring of large whales, essential for their conservation management, is feasible using noninvasive sampling within non-scientific platforms. Observed patterns are concurrent to changes of movement ecology and decline in reproductive success of the South African population, probably reflecting a large-scale restructuring of pelagic marine food webs.Charles University Grant Agency, Czech Republic.https://www.elsevier.com/locate/geccoam2023Mammal Research InstituteZoology and Entomolog