A comparison among four different retrieval methods for ice-cloud properties using data from CloudSat, CALIPSO, and MODIS

The A-Train constellation of satellites provides a new capability to measure vertical cloud profiles that leads to more detailed information on ice-cloud microphysical properties than has been possible up to now. A variational radar–lidar ice-cloud retrieval algorithm (VarCloud) takes advantage of the complementary nature of the CloudSat radar and Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) lidar to provide a seamless retrieval of ice water content, effective radius, and extinction coefficient from the thinnest cirrus (seen only by the lidar) to the thickest ice cloud (penetrated only by the radar). In this paper, several versions of the VarCloud retrieval are compared with the CloudSat standard ice-only retrieval of ice water content, two empirical formulas that derive ice water content from radar reflectivity and temperature, and retrievals of vertically integrated properties from the Moderate Resolution Imaging Spectroradiometer (MODIS) radiometer. The retrieved variables typically agree to within a factor of 2, on average, and most of the differences can be explained by the different microphysical assumptions. For example, the ice water content comparison illustrates the sensitivity of the retrievals to assumed ice particle shape. If ice particles are modeled as oblate spheroids rather than spheres for radar scattering then the retrieved ice water content is reduced by on average 50% in clouds with a reflectivity factor larger than 0 dBZ. VarCloud retrieves optical depths that are on average a factor-of-2 lower than those from MODIS, which can be explained by the different assumptions on particle mass and area; if VarCloud mimics the MODIS assumptions then better agreement is found in effective radius and optical depth is overestimated. MODIS predicts the mean vertically integrated ice water content to be around a factor-of-3 lower than that from VarCloud for the same retrievals, however, because the MODIS algorithm assumes that its retrieved effective radius (which is mostly representative of cloud top) is constant throughout the depth of the cloud. These comparisons highlight the need to refine microphysical assumptions in all retrieval algorithms and also for future studies to compare not only the mean values but also the full probability density function.

Ice crystals growing from vapor in supercooled clouds between −2.5° and −22°C: testing current parameterization methods using laboratory data

The physical and empirical relationships used by microphysics schemes to control the rate at which vapor is transferred to ice crystals growing in supercooled clouds are compared with laboratory data to evaluate the realism of various model formulations. Ice crystal growth rates predicted from capacitance theory are compared with measurements from three independent laboratory studies. When the growth is diffusion- limited, the predicted growth rates are consistent with the measured values to within about 20% in 14 of the experiments analyzed, over the temperature range −2.5° to −22°C. Only two experiments showed significant disagreement with theory (growth rate overestimated by about 30%–40% at −3.7° and −10.6°C). Growth predictions using various ventilation factor parameterizations were also calculated and compared with supercooled wind tunnel data. It was found that neither of the standard parameterizations used for ventilation adequately described both needle and dendrite growth; however, by choosing habit-specific ventilation factors from previous numerical work it was possible to match the experimental data in both regimes. The relationships between crystal mass, capacitance, and fall velocity were investigated based on the laboratory data. It was found that for a given crystal size the capacitance was significantly overestimated by two of the microphysics schemes considered here, yet for a given crystal mass the growth rate was underestimated by those same schemes because of unrealistic mass/size assumptions. The fall speed for a given capacitance (controlling the residence time of a crystal in the supercooled layer relative to its effectiveness as a vapor sink, and the relative importance of ventilation effects) was found to be overpredicted by all the schemes in which fallout is permitted, implying that the modeled crystals reside for too short a time within the cloud layer and that the parameterized ventilation effect is too strong.

Linking energy and maintenance management for sustainability through three American case studies

Purpose – The purpose of this paper is to present the findings and lessons learned from three case studies conducted for facilities located in California, North America. The findings aim to focus on energy and maintenance management practices and the interdependent link between energy and maintenance. Design/methodology/approach – The research is based on a positivist epistemological philosophical approach informed by action research. The research cycle was completed for each case study. A case study report was provided to each facility management team to foster collaboration with the researcher and to document case study process and results. Findings – Composite findings of the case studies include: there is an interdependent link between energy and maintenance management; reactive maintenance and energy management methods are commonly used; and more proactively operated and managed buildings require the interdependent link between energy maintenance management to be better understood. Research limitations/implications – The three case studies were located in California. Although the case study results can be generalized, determination of how to generalize and apply the results to commercial buildings outside of the USA is beyond the scope of this paper. Practical implications – Detailed discussion of the needs of the three facility management teams are discussed by identifying a current challenge, developing a solution and documenting lessons learned using the research cycle. Originality/value – The paper seeks to demonstrate the interdependencies of energy and maintenance management, two topics which are often researched interdependently. Additionally, the paper provides insight about maintenance management, a topic often cited as being under researched.

Identifying barriers and opportunities for transitions towards more sustainable agriculture through system analysis: the case of Vereda La Hoya, Colombia

The paper presents the results of studies which investigated farmers’ reasoning and behaviour with regards to the mis‐use of personal protective equipment and pesticide among smallholders in Colombia. First, the research approach is described. In particular, the structured mental models approach and the integrative agent‐centred framework are presented. These approaches permit to understand the farmers’ reasoning and behaviour in a system perspective. Second, the results are summarized. The methods adopted allowed not only for identifying the factors, but also the social dynamics influencing farmers. Finally, suggestions for interventions are provided, which are not limited to a technical fix, but address the underlying social causes of the problem.

Interdisciplinarity in teaching: probing urban studies

This article arises from a research project funded by the Subject Centre for Sociology, Anthropology and Politics and a literature review on ‘interdisciplinarity’ commissioned by the Subject Centre for Languages, Linguistics and Area Studies (Chettiparamb, 2007). It attempts to unpack how disciplinarity and interdisciplinarity are created through pedagogy in higher education at the module level while teaching an interdisciplinary subject such as ‘urban studies’. In particular, comparisons are made between the teaching aims and methods in two disciplines: planning and sociology. Comparisons are also made between the approach of two types of universities – a pre-1992 university and a post-1992 university. The article argues that the differences between the universities are more profound than the differences between the disciplines. The research reveals two key findings. In the pre-1992 university case study, even though the ‘contributing’ subject domains of the disciplines are similar, the disciplinary identities are maintained and accomplished in subtle ways. In contrast, in the post-1992 university, disciplinary boundaries are not so purposefully maintained, resulting in the realisation of a different construction of interdisciplinarity.

Good practice in reviewing and publishing studies on herbal medicine, with special emphasis on traditional Chinese medicine and Chinese materia medica

Ethnopharmacological relevance: Studies on traditional Chinese medicine (TCM), like those of other systems of traditional medicine (TM), are very variable in their quality, content and focus, resulting in issues around their acceptability to the global scientific community. In an attempt to address these issues, an European Union funded FP7 consortium, composed of both Chinese and European scientists and named “Good practice in traditional Chinese medicine” (GP-TCM), has devised a series of guidelines and technical notes to facilitate good practice in collecting, assessing and publishing TCM literature as well as highlighting the scope of information that should be in future publications on TMs. This paper summarises these guidelines, together with what has been learned through GP-TCM collaborations, focusing on some common problems and proposing solutions. The recommendations also provide a template for the evaluation of other types of traditional medicine such as Ayurveda, Kampo and Unani. Materials and methods: GP-TCM provided a means by which experts in different areas relating to TCM were able to collaborate in forming a literature review good practice panel which operated through e-mail exchanges, teleconferences and focused discussions at annual meetings. The panel involved coordinators and representatives of each GP-TCM work package (WP) with the latter managing the testing and refining of such guidelines within the context of their respective WPs and providing feedback. Results: A Good Practice Handbook for Scientific Publications on TCM was drafted during the three years of the consortium, showing the value of such networks. A “deliverable – central questions – labour division” model had been established to guide the literature evaluation studies of each WP. The model investigated various scoring systems and their ability to provide consistent and reliable semi-quantitative assessments of the literature, notably in respect of the botanical ingredients involved and the scientific quality of the work described. This resulted in the compilation of (i) a robust scoring system and (ii) a set of minimum standards for publishing in the herbal medicines field, based on an analysis of the main problems identified in published TCM literature.

Mid-term evaluation of African Technology Policy Studies Network Phase VI Strategic Plan: for the period January 1, 2009 to December 31, 2010

The African Technology Policy Studies Network (ATPS) is a multidisciplinary network of researchers, private sector actors, policymakers and civil society. ATPS has the vision to become the leading international centre of excellence and reference in science, technology and innovation (STI) systems research, training and capacity building, communication and sensitization, knowledge brokerage, policy advocacy and outreach in Africa. It has a Regional Secretariat in Nairobi Kenya, and operates through national chapters in 29 countries (including 27 in Africa and two Chapters in the United Kingdom and USA for Africans in the Diaspora) with an expansion plan to cover the entire continent by 2015. The ATPS Phase VI Strategic Plan aims to improve the understanding and functioning of STI processes and systems to strengthen the learning capacity, social responses, and governance of STI for addressing Africa's development challenges, with a specific focus on the Millennium Development Goals (MDGs). A team of external evaluators carried out a midterm review to assess the effectiveness and efficiency of the implementation of the Strategic Plan for the period January 1, 2009 to December 31, 2010. The evaluation methodology involved multiple quantitative and qualitative methods to assess the qualitative and quantitative inputs (human resources, financial resources, time, etc.) into ATPS activities (both thematic and facilitative) and their tangible and intangible outputs, outcomes and impacts. Methods included a questionnaire survey of ATPS members and stakeholders, key informant interviews, and focus group discussions (FGDs) with members in six countries. Effectiveness of Programmes Under all six strategic goals, very good progress has been made towards planned outputs and outcomes. This is evidenced by key performance indicators (KPIs) generated from desk review, ratings from the survey respondents, and the themes that run through the FGDs. Institutional and Programme Cost Effectiveness Institutional Effectiveness: assessment of institutional effectiveness suggests that adequate management frameworks are in place and are being used effectively and transparently. Also technical and financial accounting mechanisms are being followed in accordance with grant agreements and with global good practice. This is evidenced by KPIs generated from desk review. Programme Cost Effectiveness: assessment of cost-effectiveness of execution of programmes shows that organisational structure is efficient, delivering high quality, relevant research at relatively low cost by international standards. The evidence includes KPIs from desk review: administrative costs to programme cost ratio has fallen steadily, to around 10%; average size of research grants is modest, without compromising quality. There is high level of pro bono input by ATPS members. ATPS Programmes Strategic Evaluation ATPS research and STI related activities are indeed unique and well aligned with STI issues and needs facing Africa and globally. The multi-disciplinary and trans-boundary nature of the research activities are creating a unique group of research scientists. The ATPS approach to research and STI issues is paving the way for the so called Third Generation University (3GU). Understanding this unique positioning, an increasing number of international multilateral agencies are seeking partnership with ATPS. ATPS is seeing an increasing level of funding commitments by Donor Partners. Recommendations for ATPS Continued Growth and Effectiveness On-going reform of ATPS administrative structure to continue The on-going reforms that have taken place within the Board, Regional Secretariat, and at the National Chapter coordination levels are welcomed. Such reform should continue until fully functional corporate governance policy and practices are fully established and implemented across the ATPS governance structures. This will further strengthen ATPS to achieve the vision of being the leading STI policy brokerage organization in Africa. Although training in corporate governance has been carried out for all sectors of ATPS leadership structure in recent time, there is some evidence that these systems have not yet been fully implemented effectively within all the governance structures of the organization, especially at the Board and National chapter levels. Future training should emphasize practical application with exercises relevant to ATPS leadership structure from the Board to the National Chapter levels. Training on Transformational Leadership - Leading a Change Though a subject of intense debate amongst economists and social scientists, it is generally agreed that cultural mindsets and attitudes could enhance and/or hinder organizational progress. ATPS’s vision demands transformational leadership skills amongst its leaders from the Board members to the National Chapter Coordinators. To lead such a change, ATPS leaders must understand and avoid personal and cultural mindsets and value systems that hinder change, while embracing those that enhance it. It requires deliberate assessment of cultural, behavioural patterns that could hinder progress and the willingness to be recast into cultural and personal habits that make for progress. Improvement of relationship amongst the Board, Secretariat, and National Chapters A large number of ATPS members and stakeholders feel they do not have effective communications and/or access to Board, National Chapter Coordinators and Regional Secretariat activities. Effort should be made to improve the implementation of ATPS communication strategy to improve on information flows amongst the ATPS management and the members. The results of the survey and the FGDs suggest that progress has been made during the past two years in this direction, but more could be done to ensure effective flow of pertinent information to members following ATPS communications channels. Strategies for Increased Funding for National Chapters There is a big gap between the fundraising skills of the Regional Secretariat and those of the National Coordinators. In some cases, funds successfully raised by the Secretariat and disbursed to national chapters were not followed up with timely progress and financial reports by some national chapters. Adequate training in relevant skills required for effective interactions with STI key policy players should be conducted regularly for National Chapter coordinators and ATPS members. The ongoing training in grant writing should continue and be made continent-wide if funding permits. Funding of National Chapters should be strategic such that capacity in a specific area of research is built which, with time, will not only lead to a strong research capacity in that area, but also strengthen academic programmes. For example, a strong climate change programme is emerging at University of Nigeria Nsukka (UNN), with strong collaborations with Universities from neighbouring States. Strategies to Increase National Government buy-in and support for STI Translating STI research outcomes into policies requires a great deal of emotional intelligence, skills which are often lacking in the first and second generation universities. In the epoch of the science-based or 2GUs, governments were content with universities carrying out scientific research and providing scientific education. Now they desire to see universities as incubators of new science- or technology-based commercial activities, whether by existing firms or start-ups. Hence, governments demand that universities take an active and leading role in the exploitation of their knowledge and they are willing to make funds available to support such activities. Thus, for universities to gain the attention of national leadership they must become centres of excellence and explicit instruments of economic development in the knowledge-based economy. The universities must do this while working collaboratively with government departments, parastatals, and institutions and dedicated research establishments. ATPS should anticipate these shifting changes and devise programmes to assist both government and universities to relate effectively. New administrative structures in member organizations to sustain and manage the emerging STI multidisciplinary teams Second Generation universities (2GUs) tend to focus on pure science and often do not regard the application of their know-how as their task. In contrast, Third Generation Universities (3GUs) objectively stimulate techno-starters – students or academics – to pursue the exploitation or commercialisation of the knowledge they generate. They view this as being equal in importance to the objectives of scientific research and education. Administratively, research in the 2GU era was mainly monodisciplinary and departments were structured along disciplines. The emerging interdisciplinary scientific teams with focus on specific research areas functionally work against the current mono-disciplinary faculty-based, administrative structure of 2GUs. For interdisciplinary teams, the current faculty system is an obstacle. There is a need for new organisational forms for university management that can create responsibilities for the task of know-how exploitation. ATPS must anticipate this and begin to strategize solutions for their member institutions to transition to 3Gus administrative structure, otherwise ATPS growth will plateau, and progress achieved so far may be stunted.

Emotional well-being and adjustment to vision loss in later life: a meta-synthesis of qualitative studies.

Purpose: To review perceived emotional well-being in older people with visual impairment and perceived factors that inhibit/facilitate psychosocial adjustment to vision loss. Method: The databases of MEDLINE, EMBASE, PsycINFO and CINAHL were searched for studies published from January 1980 to December 2010, which recruited older people with irreversible vision loss, and used qualitative methods for both data collection and analysis. Results sections of the papers were synthesised using a thematic-style analysis to identify the emergent and dominant themes. Results: Seventeen qualitative papers were included in the review, and five main themes emerged from the synthesis: 1) the trauma of an ophthalmic diagnosis, 2) impact of vision loss on daily life, 3) negative impact of visual impairment on psychosocial well-being, 4) factors that inhibit social well-being, and 5) factors that facilitate psychological well-being. We found the response shift model useful for explaining our synthesis. Conclusions: Acquired visual impairment can have a significant impact on older people's well-being and make psychosocial adjustment to the condition a major challenge. Acceptance of the condition and a positive attitude facilitate successful psychosocial adjustment to vision loss as well as social support from family, friends and peers who have successfully adjusted to the condition. [Box: see text].

A process for analysis of microarray comparative genomics hybridisation studies for bacterial genomes

Background: Microarray based comparative genomic hybridisation (CGH) experiments have been used to study numerous biological problems including understanding genome plasticity in pathogenic bacteria. Typically such experiments produce large data sets that are difficult for biologists to handle. Although there are some programmes available for interpretation of bacterial transcriptomics data and CGH microarray data for looking at genetic stability in oncogenes, there are none specifically to understand the mosaic nature of bacterial genomes. Consequently a bottle neck still persists in accurate processing and mathematical analysis of these data. To address this shortfall we have produced a simple and robust CGH microarray data analysis process that may be automated in the future to understand bacterial genomic diversity. Results: The process involves five steps: cleaning, normalisation, estimating gene presence and absence or divergence, validation, and analysis of data from test against three reference strains simultaneously. Each stage of the process is described and we have compared a number of methods available for characterising bacterial genomic diversity, for calculating the cut-off between gene presence and absence or divergence, and shown that a simple dynamic approach using a kernel density estimator performed better than both established, as well as a more sophisticated mixture modelling technique. We have also shown that current methods commonly used for CGH microarray analysis in tumour and cancer cell lines are not appropriate for analysing our data. Conclusion: After carrying out the analysis and validation for three sequenced Escherichia coli strains, CGH microarray data from 19 E. coli O157 pathogenic test strains were used to demonstrate the benefits of applying this simple and robust process to CGH microarray studies using bacterial genomes.

Unraveling the electronic structures of low-valent naphthalene and anthracene iron complexes: x-ray, spectroscopic, and density functional theory studies

Naphthalene and anthracene transition metalates are potent reagents, but their electronic structures have remained poorly explored. A study of four Cp*-substituted iron complexes (Cp* = pentamethylcyclopentadienyl) now gives rare insight into the bonding features of such species. The highly oxygen- and water-sensitive compounds [K(18-crown- 6){Cp*Fe(η4-C10H8)}] (K1), [K(18-crown-6){Cp*Fe(η4-C14H10)}] (K2), [Cp*Fe(η4-C10H8)] (1), and [Cp*Fe(η4-C14H10)] (2) were synthesized and characterized by NMR, UV−vis, and 57Fe Mössbauer spectroscopy. The paramagnetic complexes 1 and 2 were additionally characterized by electron paramagnetic resonance (EPR) spectroscopy and magnetic susceptibility measurements. The molecular structures of complexes K1, K2, and 2 were determined by single-crystal X-ray crystallography. Cyclic voltammetry of 1 and 2 and spectroelectrochemical experiments revealed the redox properties of these complexes, which are reversibly reduced to the monoanions [Cp*Fe(η4-C10H8)]− (1−) and [Cp*Fe(η4-C14H10)]− (2−) and reversibly oxidized to the cations [Cp*Fe(η6-C10H8)]+ (1+) and [Cp*Fe(η6-C14H10)]+ (2+). Reduced orbital charges and spin densities of the naphthalene complexes 1−/0/+ and the anthracene derivatives 2−/0/+ were obtained by density functional theory (DFT) methods. Analysis of these data suggests that the electronic structures of the anions 1− and 2− are best represented by low-spin FeII ions coordinated by anionic Cp* and dianionic naphthalene and anthracene ligands. The electronic structures of the neutral complexes 1 and 2 may be described by a superposition of two resonance configurations which, on the one hand, involve a low-spin FeI ion coordinated by the neutral naphthalene or anthracene ligand L, and, on the other hand, a low-spin FeII ion coordinated to a ligand radical L•−. Our study thus reveals the redox noninnocent character of the naphthalene and anthracene ligands, which effectively stabilize the iron atoms in a low formal, but significantly higher spectroscopic oxidation state.

Steric effects on uranyl complexation: synthetic, structural, and theoretical studies of carbamoyl pyrazole compounds of the uranyl(VI) ion

New bifunctional pyrazole based ligands of the type [C3HR2N2CONR'] (where R = H or CH3; R' = CH3, C2H5, or (C3H7)-C-i) were prepared and characterized. The coordination chemistry of these ligands with uranyl nitrate and uranyl bis(dibenzoyl methanate) was studied with infrared (IR), H-1 NMR, electrospray-mass spectrometry (ES-MS), elemental analysis, and single crystal X-ray diffraction methods. The structure of compound [UO2(NO3)(2)(C3H3N2CON{C2H5}(2))] (2) shows that the uranium(VI) ion is surrounded by one nitrogen atom and seven oxygen atoms in a hexagonal bipyramidal geometry with the ligand acting as a bidentate chelating ligand and bonds through both the carbamoyl oxygen and pyrazolyl nitrogen atoms. In the structure of [UO2(NO3)(2)(H2O)(2)(C5H7N2CON {C2H5}(2))(2)], (5) the pyrazole figand acts as a second sphere ligand and hydrogen bonds to the water molecules through carbamoyl oxygen and pyrazolyl nitrogen atoms. The structure of [UO2(DBM)(2)C3H3N2CON{C2H5}(2)] (8) (where DBM = C6H5COCHCOC6H5) shows that the pyrazole ligand acts as a monodentate ligand and bonds through the carbamoyl oxygen to the uranyl group. The ES-MS spectra of 2 and 8 show that the ligand is similarly bonded to the metal ion in solution. Ab initio quantum chemical studies show that the steric effect plays the key role in complexation behavior.

What have dendritic cells ever done for adjuvant design? Cellular and molecular methods for the rational development of vaccine adjuvants

Our new molecular understanding of immune priming states that dendritic cell activation is absolutely pivotal for expansion and differentiation of naïve T lymphocytes, and it follows that understanding DC activation is essential to understand and design vaccine adjuvants. This chapter describes how dendritic cells can be used as a core tool to provide detailed quantitative and predictive immunomics information about how adjuvants function. The role of distinct antigen, costimulation, and differentiation signals from activated DC in priming is explained. Four categories of input signals which control DC activation – direct pathogen detection, sensing of injury or cell death, indirect activation via endogenous proinflammatory mediators, and feedback from activated T cells – are compared and contrasted. Practical methods for studying adjuvants using DC are summarised and the importance of DC subset choice, simulating T cell feedback, and use of knockout cells is highlighted. Finally, five case studies are examined that illustrate the benefit of DC activation analysis for understanding vaccine adjuvant function.

Synthesis, structural and emission studies of a bis (carbamoyl methyl) sulfone complex of uranyl nitrate

A new tri-functional ligand (Bu2NCOCH2SO2CH2CONBu2)-Bu-i-Bu-i (L) was prepared and characterized. The coordination chemistry of this ligand with uranyl nitrate was studied with IR, (HNMR)-H-1, ES-MS, TG and elemental analysis methods. The structure of the compound [UO2(NO3)(2)L] was determined by single crystal X-ray diffraction techniques. In the structure the uranium(VI) ion is surrounded by eight oxygen atoms in a hexagonal bi-pyramidal geometry. Four oxygen atoms from two nitrate groups and two oxygen atoms from the ligand form a planar hexagon. The ligand acts as a bidentate chelate and bonds through both the carbamoyl groups to the uranyl nitrate. An ES-MS spectrum shows that the complex retains the bonding in solution. The compound displayed vibronically coupled fluorescence emission.

Commodity futures prices: more evidence on forecast power, risk premia and the theory of storage

In this paper, we examine the temporal stability of the evidence for two commodity futures pricing theories. We investigate whether the forecast power of commodity futures can be attributed to the extent to which they exhibit seasonality and we also consider whether there are time varying parameters or structural breaks in these pricing relationships. Compared to previous studies, we find stronger evidence of seasonality in the basis, which supports the theory of storage. The power of the basis to forecast subsequent price changes is also strengthened, while results on the presence of a risk premium are inconclusive. In addition, we show that the forecasting power of commodity futures cannot be attributed to the extent to which they exhibit seasonality. We find that in most cases where structural breaks occur, only changes in the intercepts and not the slopes are detected, illustrating that the forecast power of the basis is stable over different economic environments.

Mapping the platelet profile for functional genomic studies and demonstration of the effect size of the GP6 locus

BACKGROUND: Evidence suggests the wide variation in platelet response within the population is genetically controlled. Unraveling the complex relationship between sequence variation and platelet phenotype requires accurate and reproducible measurement of platelet response. OBJECTIVE: To develop a methodology suitable for measuring signaling pathway-specific platelet phenotype, to use this to measure platelet response in a large cohort, and to demonstrate the effect size of sequence variation in a relevant model gene. METHODS: Three established platelet assays were evaluated: mobilization of [Ca(2+)](i), aggregometry and flow cytometry, each in response to adenosine 5'-diphosphate (ADP) or the glycoprotein (GP) VI-specific crosslinked collagen-related peptide (CRP). Flow cytometric measurement of fibrinogen binding and P-selectin expression in response to a single, intermediate dose of each agonist gave the best combination of reproducibility and inter-individual variability and was used to measure the platelet response in 506 healthy volunteers. Pathway specificity was ensured by blocking the main subsidiary signaling pathways. RESULTS: Individuals were identified who were hypo- or hyper-responders for both pathways, or who had differential responses to the two agonists, or between outcomes. 89 individuals, retested three months later using the same methodology, showed high concordance between the two visits in all four assays (r(2) = 0.872, 0.868, 0.766 and 0.549); all subjects retaining their phenotype at recall. The effect of sequence variation at the GP6 locus accounted for approximately 35% of the variation in the CRP-XL response. CONCLUSION: Genotyping-phenotype association studies in a well-characterized, large cohort provides a powerful strategy to measure the effect of sequence variation in genes regulating the platelet response.