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Showing papers by "University of Aberdeen published in 2002"


Journal ArticleDOI
TL;DR: The term 'pilot studies' refers to mini versions of a full-scale study, as well as the specific pre-testing of a particular research instrument such as a questionnaire or interview schedule.
Abstract: The term 'pilot studies' refers to mini versions of a full-scale study (also called 'feasibility' studies), as well as the specific pre-testing of a particular research instrument such as a questionnaire or interview schedule. Pilot studies are a crucial element of a good study design. Conducting a pilot study does not guarantee success in the main study, but it does increase the likelihood of success. Pilot studies fulfill a range of important functions and can provide valuable insights for other researchers. There is a need for more discussion among researchers of both the process and outcomes of pilot studies.

1,434 citations


Journal ArticleDOI
TL;DR: In this article, the authors used Giddens' theory of structuration to develop the conception of entrepreneurship as an embedded socioeconomic process and found that embeddedness plays a key role in shaping and sustaining business.

1,236 citations


Journal ArticleDOI
TL;DR: This review synthesizes current knowledge on arsenic uptake, metabolism and toxicity for arsenic resistant and nonresistant plants, including the recently discovered phenomenon of arsenic hyperaccumulation in certain fern species.
Abstract: Summary Elevation of arsenic levels in soils causes considerable concern with respect to plant uptake and subsequent entry into wildlife and human food chains. Arsenic speciation in the environment is complex, existing in both inorganic and organic forms, with interconversion between species regulated by biotic and abiotic processes. To understand and manage the risks posed by soil arsenic it is essential to know how arsenic is taken up by the roots and metabolized within plants. Some plant species exhibit phenotypic variation in response to arsenic species, which helps us to understand the toxicity of arsenic and the way in which plants have evolved arsenic resistances. This knowledge, for example, could be used produce plant cultivars that are more arsenic resistant or that have reduced arsenic uptake. This review synthesizes current knowledge on arsenic uptake, metabolism and toxicity for arsenic resistant and nonresistant plants, including the recently discovered phenomenon of arsenic hyperaccumulation in certain fern species. The reasons why plants accumulate and metabolize arsenic are considered in an evolutionary context.

1,146 citations


Journal ArticleDOI
TL;DR: This work develops methods of setting confidence limits on the estimates of abnormality, which can be used with data from normative or control samples of any size and will be most useful when the sample sizes are modest.

905 citations


Journal ArticleDOI
TL;DR: Recent large-scale surveys of yeasts isolated from blood cultures, based on standardised methodology and resistance definitions, do not support the view that antifungal resistance in pathogenic yeasts constitutes a significant or growing therapeutic problem.
Abstract: Candida albicans and related species pathogenic for man become resistant to antifungal agents, in particular triazole compounds, by expression of efflux pumps that reduce drug accumulation, alteration of the structure or concentration of antifungal target proteins, and alteration of membrane sterol composition. The clinical consequences of antifungal resistance can be seen in treatment failures in patients and in changes in the prevalences of Candida species causing disease. These effects were seen unequivocally in HIV-infected patients with oropharyngeal candida infections, but their incidence has decreased dramatically with the introduction of highly active antiretroviral therapy. The evidence for similar emergence of antifungal-resistant yeast strains and species in other types of candida infections is confounded by non-standardised susceptibility testing methods and definitions of a resistant fungal isolate. Recent large-scale surveys of yeasts isolated from blood cultures, based on standardised methodology and resistance definitions, do not support the view that antifungal resistance in pathogenic yeasts constitutes a significant or growing therapeutic problem.

749 citations


Journal ArticleDOI
TL;DR: NA DOC resulted in substantial improvement in responses to DOC, and patients with breast cancer initially failing to respond to anthracycline-based NA chemotherapy (CT) had residual tumor within axillary lymph nodes.
Abstract: PURPOSE: To compare the efficacy of neoadjuvant (NA) docetaxel (DOC) with anthracycline-based therapy and determine the efficacy of NA DOC in patients with breast cancer initially failing to respond to anthracycline-based NA chemotherapy (CT). PATIENTS AND METHODS: Patients with large or locally advanced breast cancer received four pulses of cyclophosphamide 1,000 mg/m2, doxorubicin 50 mg/m2, vincristine 1.5 mg/m2, and prednisolone 40 mg (4 × CVAP) for 5 days. Clinical tumor response was assessed. Those who responded (complete response [CR] or partial response [PR]) were randomized to receive further 4 × CVAP or 4 × DOC (100 mg/m2). All nonresponders received 4 × DOC. RESULTS: One hundred sixty-two patients were enrolled; 145 patients completed eight cycles of NA CT. One hundred two patients (66%) achieved a clinical response (PR or CR) after 4 × CVAP. After randomization, 50 patients received 4 × CVAP and 47 patients received 4 × DOC. In patients who received eight cycles of CT, the clinical CR (cCR) and...

747 citations


Journal ArticleDOI
TL;DR: The aim of this study was to review the definition and measurement of anastomotic leak after oesophagogastric, hepatopancreaticobiliary and lower gastrointestinal surgery.
Abstract: Background: Anastomotic leak after gastrointestinal surgery is an important postoperative event that leads to significant morbidity and mortality. Postoperative leak rates are frequently used as an indicator of the quality of surgical care provided. Comparison of rates between and within institutions depends on the use of standard definitions and methods of measurement of anastomotic leak. The aim of this study was to review the definition and measurement of anastomotic leak after oesophagogastric, hepatopancreaticobiliary and lower gastrointestinal surgery. Methods: A systematic review was undertaken of the published literature. Searches were carried out on five bibliographical databases (Medline, Embase, The Cochrane Library, Cumulative Index for Nursing and Allied Health Literature and HealthSTAR) for English language articles published between 1993 and 1999. Articles were critically appraised by two independent reviewers and data on definition and measurement of anastomotic leak were extracted. Results: Ninety-seven studies were reviewed and a total of 56 separate definitions of anastomotic leak were identified at three sites: upper gastrointestinal (13 definitions), hepatopancreaticobiliary (14) and lower gastrointestinal (29). The majority of studies used a combination of clinical features and radiological investigations to define and detect anastomotic leak. Conclusion: There is no universally accepted definition of anastomotic leak at any site. The definitions and values used to measure anastomotic failure vary extensively and preclude accurate comparison of rates between studies and institutions.

646 citations


Journal ArticleDOI
TL;DR: Competitive inhibition of uptake with phosphate showed that arsenite and arsenate were taken up by different uptake systems because arsenate uptake was strongly suppressed in the presence of phosphate, whereas arsenite transport was not affected by phosphate.
Abstract: Arsenic (As) finds its way into soils used for rice (Oryza sativa) cultivation through polluted irrigation water, and through historic contamination with As-based pesticides. As is known to be present as a number of chemical species in such soils, so we wished to investigate how these species were accumulated by rice. As species found in soil solution from a greenhouse experiment where rice was irrigated with arsenate contaminated water were arsenite, arsenate, dimethylarsinic acid, and monomethylarsonic acid. The short-term uptake kinetics for these four As species were determined in 7-d-old excised rice roots. High-affinity uptake (0-0.0532 mM) for arsenite and arsenate with eight rice varieties, covering two growing seasons, rice var. Boro (dry season) and rice var. Aman (wet season), showed that uptake of both arsenite and arsenate by Boro varieties was less than that of Aman varieties. Arsenite uptake was active, and was taken up at approximately the same rate as arsenate. Greater uptake of arsenite, compared with arsenate, was found at higher substrate concentration (low-affinity uptake system). Competitive inhibition of uptake with phosphate showed that arsenite and arsenate were taken up by different uptake systems because arsenate uptake was strongly suppressed in the presence of phosphate, whereas arsenite transport was not affected by phosphate. At a slow rate, there was a hyperbolic uptake of monomethylarsonic acid, and limited uptake of dimethylarsinic acid.

631 citations


Journal ArticleDOI
TL;DR: This review addresses the structural basis of TNF signalling, the pathways employed with their cellular consequences, and focuses on the specific role played by each of the two TNF receptor isotypes, TNFR1 and TNFR2.

610 citations


Journal ArticleDOI
TL;DR: Collecting normative values in an Italian normal population sample for the direct copying and delayed reproduction of the Rey-Osterrieth complex figure test revealed significant effects of age and education on performance of both copying tasks, whereas sex appeared to affect only performance on the delayed copying task.
Abstract: The Rey-Osterrieth complex figure test (ROCF) is a neuropsychological test extensively used in clinical practice to investigate visuospatial constructional functions, visuographic memory and some aspects of planning and executive function. The aim of the present study was to collect normative values in an Italian normal population sample (n=280) for the direct copying and delayed (10 min) reproduction of the ROCF. Multiple regression analysis revealed significant effects of age and education on performance of both copying tasks, whereas sex appeared to affect only performance on the delayed copying task. Inferential cut-offs have been determined and equivalent scores computed. The availability of equivalent scores for the ROCF will prove useful in clinical assessment since it allows the comparison of a subject's performance on the ROCF with that on other neuropsychological tests for which normative values collected with similar methods are already available for the Italian population.

609 citations


Journal ArticleDOI
TL;DR: Understanding the causes of pollination failure in plants can aid the successful conservation and recovery of rare plants, maintenance of crop yields, and sustainable use of wild plant resources such as forest timber.

Journal ArticleDOI
TL;DR: It is concluded that arsenate is taken up by P. vittata via the phosphate transporters, reduced to arsenite, and sequestered in the fronds primarily as As(III).
Abstract: The mechanisms of arsenic (As) hyperaccumulation in Pteris vittata , the first identified As hyperaccumulator, are unknown. We investigated the interactions of arsenate and phosphate on the uptake and distribution of As and phosphorus (P), and As speciation in P. vittata . In an 18-d hydroponic experiment with varying concentrations of arsenate and phosphate, P. vittata accumulated As in the fronds up to 27,000 mg As kg −1 dry weight, and the frond As to root As concentration ratio varied between 1.3 and 6.7. Increasing phosphate supply decreased As uptake markedly, with the effect being greater on root As concentration than on shoot As concentration. Increasing arsenate supply decreased the P concentration in the roots, but not in the fronds. Presence of phosphate in the uptake solution decreased arsenate influx markedly, whereas P starvation for 8 d increased the maximum net influx by 2.5-fold. The rate of arsenite uptake was 10% of that for arsenate in the absence of phosphate. Neither P starvation nor the presence of phosphate affected arsenite uptake. Within 8 h, 50% to 78% of the As taken up was distributed to the fronds, with a higher translocation efficiency for arsenite than for arsenate. In fronds, 49% to 94% of the As was extracted with a phosphate buffer (pH 5.6). Speciation analysis using high-performance liquid chromatography-inductively coupled plasma mass spectroscopy showed that >85% of the extracted As was in the form of arsenite, and the remaining mostly as arsenate. We conclude that arsenate is taken up by P. vittata via the phosphate transporters, reduced to arsenite, and sequestered in the fronds primarily as As(III).

Journal ArticleDOI
TL;DR: This paper examined the impact of hypercommodification on forms of spectator identification with top professional football clubs and proposed four ideal types of spectator identity: supporters, followers, fans, and flâneurs.
Abstract: World football (or soccer) has undergone an intensive hypercommodification over the past decade or so. This article examines the impact of this process on forms of spectator identification with top professional football clubs. Drawing upon previous analyses by Taylor and Critcher (on football) and the theories of Bryan Turner (on body culture), the article advances four ideal types of spectator identity: supporters, followers, fans, and flâneurs. The broad trend in sports identification is away from the supporter model (with its hot, traditional identification with local clubs) and toward the more detached, cool, consumer-orientated identification of the flâneur.

Journal ArticleDOI
TL;DR: Speciation of arsenic in tissues revealed that the predominant species present in straw was arsenate followed by arsenite and dimethylarsinic acid (DMAA), suggesting that arsenic can be readily translocated to the shoot.
Abstract: The use of arsenic (As) contaminated groundwater for irrigation of crops has resulted in elevated concentrations of arsenic in agricultural soils in Bangladesh, West Bengal (India), and elsewhere. Paddy rice (Oryza sativa L.) is the main agricultural crop grown in the arsenic-affected areas of Bangladesh. There is, therefore, concern regarding accumulation of arsenic in rice grown those soils. A greenhouse study was conducted to examine the effects of arsenic-contaminated irrigation water on the growth of rice and uptake and speciation of arsenic. Treatments of the greenhouse experiment consisted of two phosphate doses and seven different arsenate concentrations ranging from 0 to 8 mg of As L(-1) applied regularly throughout the 170-day post-transplantation growing period until plants were ready for harvesting. Increasing the concentration of arsenate in irrigation water significantly decreased plant height, grain yield, the number of filled grains, grain weight, and root biomass, while the arsenic concentrations in root, straw, and rice husk increased significantly. Concentrations of arsenic in rice grain did not exceed the food hygiene concentration limit (1.0 mg of As kg(-1) dry weight). The concentrations of arsenic in rice straw (up to 91.8 mg kg(-1) for the highest As treatment) were of the same order of magnitude as root arsenic concentrations (up to 107.5 mg kg(-1)), suggesting that arsenic can be readily translocated to the shoot. While not covered by food hygiene regulations, rice straw is used as cattle feed in many countries including Bangladesh. The high arsenic concentrations may have the potential for adverse health effects on the cattle and an increase of arsenic exposure in humans via the plant-animal-human pathway. Arsenic concentrations in rice plant parts except husk were not affected by application of phosphate. As the concentration of arsenic in the rice grain was low, arsenic speciation was performed only on rice straw to predict the risk associated with feeding contaminated straw to the cattle. Speciation of arsenic in tissues (using HPLC-ICP-MS) revealed that the predominant species present in straw was arsenate followed by arsenite and dimethylarsinic acid (DMAA). As DMAA is only present at low concentrations, it is unlikely this will greatly alter the toxicity of arsenic present in rice.

Journal ArticleDOI
TL;DR: The EORTC QLQ-C30 has become the most widely used questionnaire in Europe for cancer patients, and is extensively used around the world as mentioned in this paper. But it is not suitable for all patients.

Journal ArticleDOI
TL;DR: From the evidence presented in this review, it is believed that minimization to be a highly effective allocation method and recommend its wider adoption in the conduct of randomized controlled trials.

Journal ArticleDOI
TL;DR: Although the findings of this review may be affected by publication bias, those engaged in promoting better uptake of research information in clinical practice should consider mass media as one of the tools that may encourage the use of effective services and discourage those of unproven effectiveness.
Abstract: Mass media information on health-related issues may induce changes in health services utilisation, both through planned campaigns and unplanned coverage. Further research could target how best to compose media messages, and whether they have a different impact on members of the public and health professionals. More information is needed on whether mass media coverage brings about appropriate use of services in those patients who will benefit most. The mass media frequently cover health related topics, are the leading source of information about important health issues, and are targeted by those who aim to influence the behaviour of health professionals and patients. Objectives To assess the effects of mass media on the utilisation of health services. Randomised trials, controlled clinical trials, controlled before-and-after studies and interrupted time series analyses of mass media interventions were looked at. The participants were health care professionals, patients and the general public. Two reviewers independently extracted data and assessed study quality. Twenty studies were included. All used interrupted time series designs. Fifteen evaluated the impact of formal mass media campaigns, and five of media coverage of health-related issues. The overall methodological quality was variable. Six studies did not perform any statistical analysis, and nine used inappropriate statistical tests (ie not taking into account the effect of time trend). All of the studies apart from one concluded that mass media was effective. These positive findings were confirmed by our re-analysis in seven studies. The direction of effect was consistent across studies towards the expected change.

Journal ArticleDOI
TL;DR: A resurgence of interest in the region as a scale of economic organization has been apparent within economic geography over the past decade or so as mentioned in this paper, in view of the apparent shift towards a knowledge-based approach.
Abstract: A resurgence of interest in the region as a scale of economic organization has been apparent within economic geography over the past decade or so. In view of the apparent shift towards a ‘knowledge...

Journal ArticleDOI
TL;DR: Analysis of data from two large phase III trials demonstrates that efficacy is not compromised in patients requiring a dose reduction for adverse events, indicating that capecitabine provides a better-tolerated alternative to i.v. 5-FU/leucovorin as treatment for patients with metastatic colorectal cancer.


Journal ArticleDOI
TL;DR: The discovery of the system of cannabinoid receptors and endocannabinoids that constitutes the "endocannabinoid system" has prompted the development of CB(1)- and CB(2)-selective agonists and antagonists/inverse agonists.
Abstract: There are at least two types of cannabinoid receptors, CB(1) and CB(2), both coupled to G proteins. CB(1) receptors exist primarily on central and peripheral neurons, one of their functions being to modulate neurotransmitter release. CB(2) receptors are present mainly on immune cells. Their roles are proving more difficult to establish but seem to include the modulation of cytokine release. Endogenous agonists for cannabinoid receptors (endocannabinoids) have also been discovered, the most important being arachidonoyl ethanolamide (anandamide), 2-arachidonoyl glycerol and 2-arachidonyl glyceryl ether. Other endocannabinoids and cannabinoid receptor types may also exist. Although anandamide can act through CB(1) and CB(2) receptors, it is also a vanilloid receptor agonist and some of its metabolites may possess yet other important modes of action. The discovery of the system of cannabinoid receptors and endocannabinoids that constitutes the "endocannabinoid system" has prompted the development of CB(1)- and CB(2)-selective agonists and antagonists/inverse agonists. CB(1)/CB(2) agonists are already used clinically, as anti-emetics or to stimulate appetite. Potential therapeutic uses of cannabinoid receptor agonists include the management of multiple sclerosis/spinal cord injury, pain, inflammatory disorders, glaucoma, bronchial asthma, vasodilation that accompanies advanced cirrhosis, and cancer. Following their release onto cannabinoid receptors, endocannabinoids are removed from the extracellular space by membrane transport and then degraded by intracellular enzymic hydrolysis. Inhibitors of both these processes have been developed. Such inhibitors have therapeutic potential as animal data suggest that released endocannabinoids mediate reductions both in inflammatory pain and in the spasticity and tremor of multiple sclerosis. So too have CB(1) receptor antagonists, for example for the suppression of appetite and the management of cognitive dysfunction or schizophrenia.

Journal ArticleDOI
TL;DR: The aim was to determine the frequency and characteristics of chronic pain following open inguinal hernia repair and to identify risk factors for its development.
Abstract: Background: The aim was to determine the frequency and characteristics of chronic pain following open inguinal hernia repair and to identify risk factors for its development. Methods: This was a questionnaire survey of a historical cohort of patients who underwent inguinal hernia surgery in Aberdeen. The sample comprised all patients (n = 351) who underwent surgery between January 1995 and December 1997, and who were alive and resident in Grampian in October 1999. Outcome measures included self-report of pain persisting for more than 3 months after operation. Pain was characterized by means of the McGill Pain Questionnaire, and quality of life was assessed with the Short Form 36 (SF-36). Results: A total of 226 patients (64 per cent) completed the questionnaire, 67 (30 per cent) of whom reported chronic pain. Reported pain was predominantly neuropathic in character. Patients at increased risk of chronic pain were under 40 years old (P < 0.001), had day-case surgery (P = 0.004), had subsequent surgery on the same side (P < 0.005) and recalled pain before operation (P = 0.005). The SF-36 scores were significantly different in the social functioning, mental health and pain dimensions in patients with chronic pain. Conclusion: Chronic pain occurred in 30 per cent of patients after open hernia repair, a higher frequency than has been reported previously. Several risk factors were identified and further prospective research is recommended.

Journal ArticleDOI
TL;DR: There is an imperfect evidence base to support decisions regarding strategies that are likely to be appropriate and effective under varying circumstances, and further research is required to explore determinants of provider behavior.
Abstract: Health services research consistently demonstrates a gap between research-based best clinical practice and what doctors actually do. Traditionally, the profession of medicine has behaved as if dissemination of research findings in peer-reviewed journals will eliminate this gap, even though professionals typically have less than 1 hour per week to read. This problem is complicated by the fact that physicians have not been trained generally to appraise published research, which is of variable quality in any event. Physicians interested in changing their practices also encounter organizational, peer group, and individual barriers at the same time as they face information overload and patient expectations. In a word, physicians' abilities to manage information is overwhelmed. This article both summarizes initiatives to improve physicians' information management through efforts to synthesize available evidence and describes the current evidence base of effectiveness and efficiency of dissemination and implementation strategies. We conclude that there is an imperfect evidence base to support decisions regarding strategies that are likely to be appropriate and effective under varying circumstances. Since this problem is compounded by the lack of a theoretical base for conceptualizing physician behavior change, we suggest exploring the applicability of behavioral theories to the understanding of professional behavior change. We also suggest exploring the use of theory-based process evaluations alongside randomized trials of dissemination and implementation strategies to further test theories and to explore causal mechanisms. Further research is required to explore determinants of provider behavior to better identify modifiable and non-modifiable effect modifiers, to develop methods of identifying barriers and facilitators to change, and to estimate the efficiency of dissemination and implementation strategies in the presence of different barriers and effect modifiers.

Journal ArticleDOI
TL;DR: A high success rate is achieved when low‐dose aspirin is used for antiphospholipid syndrome in pregnancy, and the addition of low molecular weight heparin does not significantly improve pregnancy outcome.

Journal ArticleDOI
TL;DR: It is argued that no simple, universal relationship can be drawn between morphology and the invasive potential of a fungus and it is necessary to characterise the morphology of the fungus at different stages and locations during the natural history of a disease.

Journal ArticleDOI
01 Jan 2002-Oryx
TL;DR: A review of the more general issues relating to bat conservation highlights the priority areas where action is needed immediately at a global, regional or national level and highlights in particular the global importance of islands and caves for bats.
Abstract: makers as well as organisations and individuals who are promoting bat conservation issues. The underlying lights the priority areas where action is needed immediately at a global, regional or national level. It highlights threat to bats is pressure on resources from increasing human populations that leads to the loss or modification in particular the global importance of islands and caves for bats. of foraging habitats and roosts. Bats frequently have a negative public image that influences the response to the problems of rabies and vampire bats in Latin America Keywords Action Plan, bats, caves, Chiroptera, conservation priorities, islands. and conflicts between bats and commercial fruit growers in other areas of the world. In some areas bats are

Journal ArticleDOI
TL;DR: It is only through its quirky tumour-killing characteristic that TNF cytokine was first identified and may still hold the key to effective tumour therapy and the majority of information has been gained about TNF.
Abstract: It had been known for some time that tumour masses which had become contaminated by a bacterial infection would on occasion regress and disappear. It was thought that the bacteria were releasing a factor which would make the tumour necrotic and whither. This factor was termed tumour necrosis factor (TNF) (Old, 1985). It was not until more recent advances in immunology that it became clear that antigens from the bacterial invader (notably lipopolysaccharide LPS) were causing the release of the patient's own TNF which could cause the tumour regression. The hunt was on to isolate this TNF which could be used as a magic therapy to control cancer cell growth and persistence, plus enhance the academic understanding of the ways by which a cell could die. It was discovered that TNF and lymphotoxin (LT) were products from macrophages and lymphocytes that were capable of lysing many cell types including some tumour cells (Carswell et al., 1975; Granger et al., 1969). TNF was also found to be identical to the protein cachectin, which was known to be involved in the fever and muscle wastage seen in cancer patients (Beutler et al., 1985). Hence, the role TNF played in a range of physiological actions was important and the hunt was on to identify TNF and related molecules such as LT. Modern techniques have since allowed the isolation, characterization and cloning of the genes for TNF which is structurally related to LT plus an expanding family of TNF-like ligands (Table 1). These cytokine molecules include ligands such as Fas, CD40 and RANK which cause wide-ranging long-term cellular activities in cells such as differentiation, proliferation or death. Evolution has created this TNF superfamily of cytokines to control and manipulate the immune system, modulating processes such as haematopoiesis, antibody production, or short- and long-term immunity. It is only through its quirky tumour-killing characteristic that TNF cytokine was first identified and may still hold the key to effective tumour therapy. As the majority of information has been gained about TNF and it is the archetypal cytokine of the superfamily, displaying the greatest range of cellular actions, this review will focus on the molecular aspects and biological role of TNF signalling. Table 1 TNF ligand superfamily

Journal ArticleDOI
TL;DR: Level Solving problems by reasoning uses mental resources to create mental model of problem and to work out solution from ®rst principles Supervisor level Supervisory control Allocates attention and mental resources Resource management level Resource management uses available resources, information, equipment and personnel to manage perioperative care of patient.
Abstract: level Solving problems by reasoning Uses mental resources to create mental model of problem and to work out solution from ®rst principles Supervisor level Supervisory control Allocates attention and mental resources Resource management level Resource management Uses available resources, information, equipment and personnel to manage perioperative care of patient Fletcher et al.

Journal ArticleDOI
TL;DR: A checklist for reporting and appraising studies of genotype prevalence and studies of gene-disease associations was developed and focuses on selection of study subjects, analytic validity of genotyping, population stratification, and statistical issues.
Abstract: The recent completion of the first draft of the human genome sequence and advances in technologies for genomic analysis are generating tremendous opportunities for epidemiologic studies to evaluate the role of genetic variants in human disease. Many methodological issues apply to the investigation of variation in the frequency of allelic variants of human genes, of the possibility that these influence disease risk, and of assessment of the magnitude of the associated risk. Based on a Human Genome Epidemiology workshop, a checklist for reporting and appraising studies of genotype prevalence and studies of gene-disease associations was developed. This focuses on selection of study subjects, analytic validity of genotyping, population stratification, and statistical issues. Use of the checklist should facilitate the integration of evidence from these studies. The relation between the checklist and grading schemes that have been proposed for the evaluation of observational studies is discussed. Although the limitations of grading schemes are recognized, a robust approach is proposed. Other issues in the synthesis of evidence that are particularly relevant to studies of genotype prevalence and gene-disease association are discussed, notably identification of studies, publication bias, criteria for causal inference, and the appropriateness of quantitative synthesis.

Journal ArticleDOI
TL;DR: Progress with the identification of QTLs for drought resistance-related traits in rice is summarized here with the emphasis on a mapping population of a cross between drought-resistant varieties Azucena and Bala.
Abstract: The advent of saturated molecular maps promised rapid progress towards the improvement of crops for genetically complex traits like drought resistance via analysis of quantitative trait loci (QTL). Progress with the identification of QTLs for drought resistance-related traits in rice is summarized here with the emphasis on a mapping population of a cross between drought-resistant varieties Azucena and Bala. Data which have used root morphological traits and indicators of drought avoidance in field-grown plants are reviewed, highlighting problems and uncertainties with the QTL approach. The contribution of root-growth QTLs to drought avoidance appears small in the experiments so far conducted, and the limitations of screening methodologies and the involvement of shoot-related mechanisms of drought resistance are studied. When compared to Azucena, Bala has been observed to have highly sensitive stomata, does not roll its leaves readily, has a greater ability to adjust osmotically, slows growth more rapidly when droughted and has a lower water-use efficiency. It is also a semi-dwarf variety and hence has a different canopy structure. There is a need to clarify the contribution of the shoot to drought resistance from the level of the biochemistry of photosynthesis through stomatal behaviour and leaf anatomy to canopy architecture. Recent advances in studying the physical and biochemical processes related to water use and drought stress offer the opportunity to advance a more holistic understanding of drought resistance. These include the potential use of infrared thermal imaging to study energy balance, integrated and online stable isotope analysis to dissect processes involved in carbon dioxide fixation and water evaporation, and leaf fluorescence to monitor photosynthesis and photochemical quenching. Justification and a strategy for this integrated approach is described, which has relevance to the study of drought resistance in most crops.