Comparing correlations of continuous observations from two independent populations using a sequential approach

A sequential study design generally makes more efficient use of available information than a fixed sample counterpart of equal power. This feature is gradually being exploited by researchers in genetic and epidemiological investigations that utilize banked biological resources and in studies where time, cost and ethics are prominent considerations. Recent work in this area has focussed on the sequential analysis of matched case-control studies with a dichotomous trait. In this paper, we extend the sequential approach to a comparison of the associations within two independent groups of paired continuous observations. Such a comparison is particularly relevant in familial studies of phenotypic correlation using twins. We develop a sequential twin method based on the intraclass correlation and show that use of sequential methodology can lead to a substantial reduction in the number of observations without compromising the study error rates. Additionally, our approach permits straightforward allowance for other explanatory factors in the analysis. We illustrate our method in a sequential heritability study of dysplasia that allows for the effect of body mass index and compares monozygotes with pairs of singleton sisters. Copyright (c) 2006 John Wiley & Sons, Ltd.

A middleware independent grid workflow builder for scientific applications

Grid workflow authoring tools are typically specific to particular workflow engines built into Grid middleware, or are application specific and are designed to interact with specific software implementations. g-Eclipse is a middleware independent Grid workbench that aims to provide a unified abstraction of the Grid and includes a Grid workflow builder to allow users to author and deploy workflows to the Grid. This paper describes the g-Eclipse Workflow Builder and its implementations for two Grid middlewares, gLite and GRIA, and a case study utilizing the Workflow Builder in a Grid user's scientific workflow deployment.

Environmental variation at the onset of independent foraging affects full-grown body mass in the red fox

The period following the withdrawal of parental care has been highlighted as a key developmental period for juveniles. One reason for this is that juveniles cannot forage as competently as adults, potentially placing them at greater risk from environmentally-induced changes in food availability. However, no study has examined this topic. Using a long-term dataset on red foxes (Vulpes vulpes), we examined (i) dietary changes that occurred in the one-month period following the attainment of nutritional independence, (ii) diet composition in relation to climatic variation, and (iii) the effect of climatic variation on subsequent full-grown mass. Diet at nutritional independence contained increased quantities of easy-to-catch food items (earthworms and insects) when compared with pre-independence. Interannual variation in the volume of rainfall at nutritional independence was positively correlated to the proportion of earthworms in cub diet. Pre-independence cub mass and rainfall immediately following nutritional independence explained a significant proportion of variance in full-grown mass, with environmental variation affecting full-grown mass of the entire cohorts. Thus, weather-mediated availability of easy-to-catch food items at a key developmental stage has lifelong implications for the development of juvenile foxes by affecting full-grown mass, which in turn appears to be an important component of individual reproductive potential.

CCL3, acting via the chemokine receptor CCR5, leads to independent activation of Janus kinase 2 (JAK2) and G(i) proteins

The interaction of the chemokine receptor, CCR5, expressed in recombinant cells, with different G proteins was investigated and CCR5 was found to interact with G(i), G(o) and G(q) species. Interaction with Gi leads to G protein activation, whereas G. does not seem to be activated. Additionally, CCR5 activation also leads to phosphorylation of Janus kinase 2 (JAK2). Activation of JAK2 is independent of Gi or Gq activation. Gi protein activation was not prevented by inhibition of JAK, showing that heterotrimeric G protein activation and activation of the JAK/signal transducer and activator of transcription (STAT) pathway are independent of each other. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Subcontract and supply enquiries in the tender process of contractors

In the tender process, contractors often rely on subcontract and supply enquiries to calculate their bid prices. However, this integral part of the bidding process is not empirically articulated in the literature. Over 30 published materials on the tendering process of contractors that talk about enquiries were reviewed and found to be based mainly on experiential knowledge rather than systematic evidence. The empirical research here helps to describe the process of enquiries precisely, improve it in practice, and have some basis to support it in theory. Using a live participant observation case study approach, the whole tender process was shadowed in the offices of two of the top 20 UK civil engineering construction firms. This helped to investigate 15 research questions on how contractors enquire and obtain prices from subcontractors and suppliers. Forty-three subcontract enquiries and 18 supply enquiries were made across two different projects with average value of 7m. An average of 15 subcontract packages and seven supply packages was involved. Thus, two or three subcontractors or suppliers were invited to bid in each package. All enquiries were formulated by the estimator, with occasional involvement of three other personnel. Most subcontract prices were received in an average of 14 working days; and supply prices took five days. The findings show 10 main activities involved in processing enquiries and their durations, as well as wasteful practices associated with enquiries. Contractors should limit their enquiry invitations to a maximum of three per package, and optimize the waiting time for quotations in order to improve cost efficiency.

Commercial reviews in the tender process of contractors

Purpose – The purpose of this paper is to show the extent to which clients amend standard form contracts in practice, the locus of the amendments, and how contractors respond to the amendments when putting together a bid. Design/methodology/approach – Four live observational case studies were carried out in two of the top 20 UK construction firms. The whole process used to review the proposed terms and conditions of the contract was shadowed using participant observation, interview and documentary analysis. Findings – All four cases showed strong evidence of amendments relating mostly to payment and contractual aspects: 83 amendments in Case Study 1 (CS1), 80 in CS2, 15 in CS3 and 29 in CS4. This comprised clauses that were modified (37 per cent), substituted (23 per cent), deleted (7 per cent) and new additions (33 per cent). Risks inherent in the amendments were mostly addressed through contractual rather than price mechanisms, to reflect commercial imperatives. “Qualifications” and “clarifications” were included in the tender submissions for post-tender negotiations. Thus, the amendments did not necessarily influence price. There was no evidence of a “standard-form contract“ being used as such, although clients may draw on published “standard-form contracts” to derive the forms of contract actually used in practice. Practical implications – Contractors should pay attention to clauses relating to contractual and financial aspects when reviewing tender documents. Clients should draft equitable payment and contractual terms and conditions to reduce risk of dispute. Indeed, it is prudent for clients not to pass on inestimable risks. Originality/value – A better understanding of the extent and locus of amendments in standard form contracts, and how contractors respond, is provided.

How contractors price risk in bids: theory and practice

Formal and analytical models that contractors can use to assess and price project risk at the tender stage have proliferated in recent years. However, they are rarely used in practice. Introducing more models would, therefore, not necessarily help. A better understanding is needed of how contractors arrive at a bid price in practice, and how, and in what circumstances, risk apportionment actually influences pricing levels. More than 60 proposed risk models for contractors that are published in journals were examined and classified. Then exploratory interviews with five UK contractors and documentary analyses on how contractors price work generally and risk specifically were carried out to help in comparing the propositions from the literature to what contractors actually do. No comprehensive literature on the real bidding processes used in practice was found, and there is no evidence that pricing is systematic. Hence, systematic risk and pricing models for contractors may have no justifiable basis. Contractors process their bids through certain tendering gateways. They acknowledge the risk that they should price. However, the final settlement depends on a set of complex, micro-economic factors. Hence, risk accountability may be smaller than its true cost to the contractor. Risk apportionment occurs at three stages of the whole bid-pricing process. However, analytical approaches tend not to incorporate this, although they could.

Critical success factors for competitiveness of contractors: A China study

Gaining or maintaining a “contractor's” competitive advantage is not easy as it is determined by a large number of factors. Identification of critical success factors (CSFs) allows one to reduce the vast number of factors to some manageable few but vital ones. Based on the CSFs, contractors' limited resources such as money and manpower can be allocated and aligned appropriately for yielding a maximum outcome of overall competitiveness. This paper describes the CSFs identified from a survey study carried out in Mainland China. The ranking analysis of the survey results shows that 35 factors are rated as critical for determining the competitiveness of a contractor. Factor analysis reveals that the 35 CSFs identified can be grouped into eight clusters, namely, project management skills, organization structure, resources, competitive strategy, relationships, bidding, marketing, and technology. The CSFs in this study provide a vehicle for guiding a contractor in managing its resources in order to improve competitive advantage. The study also provides insights into the management of competitiveness for contractors that are operating in the particular context of the Chinese construction industry.

International construction and Brazilian contractors’ operations

The international construction market is very complex, and requires strong structure and strategy for companies wanting to operate overseas. This article investigates characteristics of international construction. The international operation of Brazilian contractors is explored via results from a qualitative study which was carried out using case studies. The case studies comprised ten big Brazilian contractors, six of which operate abroad. The study identified the patterns of international operation, the competitive advantages of these contractors, as well as the difficulties faced by them in the international construction market. Four of the contractors studied operate only in the domestic market. The study of these cases revealed both obstacles and motivations for future international operations. The study revealed that despite the existing competitive advantages, Brazilian contractors' presence in the international market is limited. The main reason for that is probably their main competitive disadvantage: the lack of financial support from the government.

Moderate Champagne consumption promotes an acute improvement in acute endothelial-independent vascular function in healthy human volunteers

Epidemiological studies have suggested an inverse correlation between red wine consumption and the incidence of CVD. However, Champagne wine has not been fully investigated for its cardioprotective potential. In order to assess whether acute and moderate Champagne wine consumption is capable of modulating vascular function, we performed a randomised, placebo-controlled, cross-over intervention trial. We show that consumption of Champagne wine, but not a control matched for alcohol, carbohydrate and fruit-derived acid content, induced an acute change in endothelium-independent vasodilatation at 4 and 8 h post-consumption. Although both Champagne wine and the control also induced an increase in endothelium-dependent vascular reactivity at 4 h, there was no significant difference between the vascular effects induced by Champagne or the control at any time point. These effects were accompanied by an acute decrease in the concentration of matrix metalloproteinase (MMP-9), a significant decrease in plasma levels of oxidising species and an increase in urinary excretion of a number of phenolic metabolites. In particular, the mean total excretion of hippuric acid, protocatechuic acid and isoferulic acid were all significantly greater following the Champagne wine intervention compared with the control intervention. Our data suggest that a daily moderate consumption of Champagne wine may improve vascular performance via the delivery of phenolic constituents capable of improving NO bioavailability and reducing matrix metalloproteinase activity.

Age-related increases in circulating inflammatory markers in men are independent of BMI, blood pressure and blood lipid concentrations

Objective: To examine whether age-related increase in concentrations of circulating inflammatory mediators is due to concurrent increases in cardiovascular risk factors or is independent of these. Methods and results: Cytokines (IL-6, IL-18), chemokines (6Ckine, MCP-1, IP-10), soluble adhesion molecules (sICAM-1, sVCAM-1, sE-selectin) and adipokines (adiponectin) were measured in the plasma of healthy male subjects aged 18-84 years (n = 162). These were related to known cardiovascular risk factors (age, BMI, systolic and diastolic blood pressure, plasma total cholesterol, LDL cholesterol, HDL cholesterol and triacylglycerol concentrations) in order to identify significant associations. Plasma concentrations of sVCAM-1, sE-selectin, IL-6, IL-18, MCP-1, 6Ckine, IP-10 and adiponectin, but not sICAM-1, were significantly positively correlated with age, as well as with several other cardiovascular risk factors. The correlations with other risk factors disappeared when age was controlled for. In contrast, the correlations with age remained significant for sVCAM-1, IL-6, MCP-1, 6Ckine and IP-10 when other cardiovascular risk factors were controlled for. Conclusions: Plasma concentrations of some inflammatory markers (sVCAM-1, IL-6, MCP-L 6Ckine, IP-10) are positively correlated with age, independent of other cardiovascular risk factors. This suggests that age-related inflammation may not be driven by recognised risk factors. (C) 2006 Elsevier Ireland Ltd. All rights reserved.

Neuroprotective effects of hesperetin in mouse primary neurones are independent of CREB activation

Dietary flavonoids, including the citrus flavanone hesperetin, may have stimulatory, effects on cytoprotective intracellular signalling pathways. In primary mouse cortical neurone cultures, but not SH-SY5Y human neuroblastoma cells or human primary dermal fibroblasts (Promocells), hesperetin (100-300 nM, 15 min) caused significant increases in the level of ERK1/2 phosphorylation, but did not increase CREB phosphorylation. Administration of hesperetin for 18 h did not alter gene expression driven by the cyclic AMP response element (CRE), assessed using a luciferase reporter system, but 300 nM hesperetin partially reversed staurosporine-induced cell death in primary neurones. Our data show that hesperetin is a neuroprotective compound at concentrations where antioxidant effects are unlikely to predominate. The effects of hesperetin are cell-type dependent and, unlike the flavanol (-)epicatechin, neuroprotection in vitro is not associated with enhanced CREB phosphorylation or CRE-mediated gene expression. (C) 2008 Elsevier Ireland Ltd. All rights reserved.