Predictive genetic test decisions for Huntington's disease: context, appraisal and new moral imperatives

Predictive testing is one of the new genetic technologies which, in conjunction with developing fields such as pharmacogenomics, promises many benefits for preventive and population health. Understanding how individuals appraise and make genetic test decisions is increasingly relevant as the technology expands. Lay understandings of genetic risk and test decision-making, located within holistic life frameworks including family or kin relationships, may vary considerably from clinical representations of these phenomena. The predictive test for Huntington's disease (HD), whilst specific to a single-gene, serious, mature-onset but currently untreatable disorder, is regarded as a model in this context. This paper reports upon a qualitative Australian study which investigated predictive test decision-making by individuals at risk for HD, the contexts of their decisions and the appraisals which underpinned them. In-depth interviews were conducted in Australia with 16 individuals at 50% risk for HD, with variation across testing decisions, gender, age and selected characteristics. Findings suggested predictive testing was regarded as a significant life decision with important implications for self and others, while the right not to know genetic status was staunchly and unanimously defended. Multiple contexts of reference were identified within which test decisions were located, including intra- and inter-personal frameworks, family history and experience of HID, and temporality. Participants used two main criteria in appraising test options: perceived value of, or need for the test information, for self and/or significant others, and degree to which such information could be tolerated and managed, short and long-term, by self and/or others. Selected moral and ethical considerations involved in decision-making are examined, as well as the clinical and socio-political contexts in which predictive testing is located. The paper argues that psychosocial vulnerabilities generated by the availability of testing technologies and exacerbated by policy imperatives towards individual responsibility and self-governance should be addressed at broader societal levels. (C) 2003 Elsevier Science Ltd. All rights reserved.

Statistical modeling and projections of lung cancer mortality in 4 industrialized countries

The purpose of this work was to model lung cancer mortality as a function of past exposure to tobacco and to forecast age-sex-specific lung cancer mortality rates. A 3-factor age-period-cohort (APC) model, in which the period variable is replaced by the product of average tar content and adult tobacco consumption per capita, was estimated for the US, UK, Canada and Australia by the maximum likelihood method. Age- and sex-specific tobacco consumption was estimated from historical data on smoking prevalence and total tobacco consumption. Lung cancer mortality was derived from vital registration records. Future tobacco consumption, tar content and the cohort parameter were projected by autoregressive moving average (ARIMA) estimation. The optimal exposure variable was found to be the product of average tar content and adult cigarette consumption per capita, lagged for 2530 years for both males and females in all 4 countries. The coefficient of the product of average tar content and tobacco consumption per capita differs by age and sex. In all models, there was a statistically significant difference in the coefficient of the period variable by sex. In all countries, male age-standardized lung cancer mortality rates peaked in the 1980s and declined thereafter. Female mortality rates are projected to peak in the first decade of this century. The multiplicative models of age, tobacco exposure and cohort fit the observed data between 1950 and 1999 reasonably well, and time-series models yield plausible past trends of relevant variables. Despite a significant reduction in tobacco consumption and average tar content of cigarettes sold over the past few decades, the effect on lung cancer mortality is affected by the time lag between exposure and established disease. As a result, the burden of lung cancer among females is only just reaching, or soon will reach, its peak but has been declining for I to 2 decades in men. Future sex differences in lung cancer mortality are likely to be greater in North America than Australia and the UK due to differences in exposure patterns between the sexes. (c) 2005 Wiley-Liss, Inc.

Understanding the phylogeographic patterns of European hedgehogs, Erinaceus concolor and E-europaeus using the MHC

The genome of the European hedgehog, Erinaceus concolor and E. europaeus, shows a strong signal of cycles of restriction to glacial refugia and postglacial expansion. Patterns of expansion, however, differ for mitochondrial DNA (mtDNA) and preliminary analysis of nuclear markers. In this study, we determine phylogeographic patterns in the hedgehog using two loci of the major histocompatibility complex (MHC), isolated for the first time in hedgehogs. These genes show long persistence times and high polymorphism in many species because of the actions of balancing selection. Among 84 individuals screened for variation, only two DQA alleles were identified in each species, but 10 DQB alleles were found in E. concolor and six in E. europaeus. A strong effect of demography on patterns of DQB variability is observed, with only weak evidence of balancing selection. While data from mtDNA clearly subdivide both species into monophyletic subgroups, the MHC data delineate only E. concolor into distinct subgroups, supporting the preliminary findings of other nuclear markers. Together with differences in variability, this suggests that the refugia history and/or expansion patterns of E. concolor and E. europaeus differ.

Development and evaluation of the Clinician Suicide Risk Assessment Checklist

This paper describes the development and evaluation of a new instrument – the Clinician Suicide Risk Assessment Checklist (CSRAC). The instrument assesses the clinician’s competency in three areas: clinical interviewing, assessment of specific suicide risk factors, and formulating a management plan. A draft checklist was constructed by integrating information from 1) literature review 2) expert clinician focus group and 3) consultation with experts. It was utilised in a simulated clinical scenario with clinician trainees and a trained actor in order to test for inter-rater agreement. Agreement was calculated and the checklist was re-drafted with the aim of maximising agreement. A second phase of simulated clinical scenarios was then conducted and inter-rater agreement was calculated for the revised checklist. In the first phase of the study, 18 of 35 items had inadequate inter-rater agreement (60%>), while in the second phase, using the revised version, only 3 of 39 items failed to achieve adequate inter-rater agreement. Further evidence of reliability and validity are required. Continued development of the CSRAC will be necessary before it can be utilised to assess the effectiveness of risk assessment training programs.

Dietary patterns and metabolic syndrome - a review of epidemiologic evidence

Metabolic syndrome is associated with increased risk of coronary heart disease and type 2 diabetes, and appears to be widely prevalent in both developed and developing countries. While lifestyle modification is recommended for management of the syndrome, the dietary pattern most beneficial for patients is yet to be ascertained. Original research papers from the Medline database were examined for dietary patterns that may be associated with the syndrome. Three large-scale epidemiological studies were found fitting our criteria. Dietary patterns high in fruit and vegetable content were generally found to be associated with lower prevalence of metabolic syndrome. Diet patterns with high meat intake were frequently associated with components of metabolic syndrome, particularly impaired glucose tolerance. High dairy intake was generally associated with reduced risk for components of metabolic syndrome with some inconsistency in the literature regarding risk of obesity. Minimally processed cereals appeared to be associated with decreased risk of metabolic syndrome, while highly processed cereals with high glycaemic index are associated with higher risk. Fried foods were noticeably absent from any dietary pattern associated with decreased prevalence of metabolic syndrome. The conclusion of this review is that no individual dietary component could be considered wholly responsible for the association of diet with metabolic syndrome. Rather it is the overall quality of the diet that appears to offer protection against lifestyle disease such as metabolic syndrome. Further research is required into conditions, such as overweight and obesity, which may influence the effect of diet on the development of metabolic syndrome.

Comparison of the reintroduced MEIA (R) assay with HPLC-MS/MS for the determination of whole-blood sirolimus from transplant recipients

Therapeutic monitoring with dosage individualization of sirolimus drug therapy is standard clinical practice for organ transplant recipients. For several years sirolimus monitoring has been restricted as a result of lack of an immunoassay. The recent reintroduction of the microparticle enzyme immunoassay (MEIA (R)) for sirolimus on the IMx (R) analyser has the potential to address this situation. This Study, using patient samples, has compared the MEIA (R) sirolimus method with an established HPLC-tandem mass spectrometry method (HPLC-MS/MS). An established HPLC-UV assay was used for independent cross-validation. For quality control materials (5, 11, 22 mu g/L), the MEIA (R) showed acceptable validation criteria based on intra-and inter-run precision (CV) and accuracy (bias) of < 8% and < 13%, respectively. The lower limit of quantitation was found to be approximately 3 mu g/L. The performance of the immunoassay was compared with HPLC-MS/MS using EDTA whole-blood samples obtained from various types of organ transplant recipients (n = 116). The resultant Deming regression line was: MEIA = 1.3 x HPLC-MS/MS+ 1.3 (r = 0.967, s(y/x) = 1) with a mean bias of 49.2% +/- 23.1 % (range, -2.4% to 128%; P < 0.001). The reason for the large and variable bias was not explored in this study, but the sirolimus-metabolite cross-reactivity with the MEIA (R) antibody could be a substantive contributing factor. Whereas the MEIA (R) sirolimus method may be an adjunct to sirolimus dosage individualization in transplant recipients, users must consider the implications of the substantial and variable bias when interpreting results. In selected patients where difficult clinical issues arise, reference to a specific chromatographic method may be required.

Quadriceps activity and movement reactions in response to unpredictable sagittal support-surface translations in women with patellofemoral pain

Patellofemoral pain (PFP) may be related to unfavorable knee joint loading. Delayed and/or reduced activity of vastus medialis obliquus (VMO) and different movement patterns have been identified in individuals with PFP in some studies, whereas other studies have failed to show a difference compared to non-affected controls. The discrepancy between study results may depend on the different tasks that have been investigated. No previous study has investigated these variables in postural responses to unpredictable perturbations in PFP. Whole body three dimensional kinematics and surface EMG of quadriceps muscles activation was studied in postural responses to unpredictable support surface translations in 17 women with PFP who were pain free at the time of testing, and 17 matched healthy controls. The results of the present study showed earlier onset of VMO activity and associated changes in kinematics to anterior platform translation in the PFP subjects. We suggest that the relative timing between the portions quadriceps muscles may be task specific and part of an adapted response in attempt to reduce knee joint loading. This learned response appears to remain even when the pain is no longer present.

Modelling the conversion of Colombian lowland ecosystems since 1940: Drivers, patterns and rates

In biologically mega-diverse countries that are undergoing rapid human landscape transformation, it is important to understand and model the patterns of land cover change. This problem is particularly acute in Colombia, where lowland forests are being rapidly cleared for cropping and ranching. We apply a conceptual model with a nested set of a priori predictions to analyse the spatial and temporal patterns of land cover change for six 50-100 km(2) case study areas in lowland ecosystems of Colombia. Our analysis included soil fertility, a cost-distance function, and neighbourhood of forest and secondary vegetation cover as independent variables. Deforestation and forest regrowth are tested using logistic regression analysis and an information criterion approach to rank the models and predictor variables. The results show that: (a) overall the process of deforestation is better predicted by the full model containing all variables, while for regrowth the model containing only the auto-correlated neighbourhood terms is a better predictor; (b) overall consistent patterns emerge, although there are variations across regions and time; and (c) during the transformation process, both the order of importance and significance of the drivers change. Forest cover follows a consistent logistic decline pattern across regions, with introduced pastures being the major replacement land cover type. Forest stabilizes at 2-10% of the original cover, with an average patch size of 15.4 (+/- 9.2) ha. We discuss the implications of the observed patterns and rates of land cover change for conservation planning in countries with high rates of deforestation. (c) 2005 Elsevier Ltd. All rights reserved.

Mud, algae or seagrass: An assessment of remote sensing techniques for mapping inter-tidal seagrass cover and composition in turbid tropical environments

Large areas of tropical sub- and inter-tidal seagrass beds occur in highly turbid environments and cannot be mapped through the water column. The purpose of this project was to determine if and how airborne and satellite imaging systems could be used to map inter-tidal seagrass properties along the wet-tropics coast in north Queensland, Australia. The work aimed to: (1) identify the minimum level of seagrass foliage cover that could be detected from airborne and satellite imagery; and (2) define the minimum detectable differences in seagrass foliage cover in exposed intertidal seagrass beds. High resolution spectral-reflectance data (2040 bands, 350 – 2500nm) were collected over 40cm diameter plots from 240 sites on Magnetic Island, Pallarenda Beach and Green Island in North Queensland at spring low tides in April 2006. The seagrass species sampled were: Thalassia hemprechii, Halophila ovalis, Halodule uninerivs; Syringodium isoetifolium, Cymodocea serrulata, and Cymodoea rotundata. Digital photos were captured for each plot and used to derive estimates of seagrass species cover, epiphytic growth, micro- and macro-algal cover, and substrate colour. Sediment samples were also collected and analysed to measure the concentration of Chlorophyll-a associated with benthic micro-algae. The field reflectance spectra were analysed in combination with their corresponding seagrass species foliage cover levels to establish the minimum foliage projective cover required for each seagrass to be significantly different from bare substrate and substrate with algal cover. This analysis was repeated with reflectance spectra resampled to the bandpass functions of Quickbird, Ikonos, SPOT 5 and Landsat 7 ETM. Preliminary results indicate that conservative minimum detectable seagrass cover levels across most the species sampled were between 30%- 35% on dark substrates. Further analysis of these results will be conducted to determine their separability and satellite images and to assess the effects epiphytes and algal cover.

Antecedents of task-specific goal orientation: An investigation of task practice, personality and global goal orientation

Goal orientation, a mental framework for understanding how individuals approach learning and achievement situations, has emerged as an important topic in organisational psychology. This study investigated the effects of task practice, personality (openness to experience and neuroticism), and global goal orientation (predisposition to adopt a certain response pattern across all domains) on participants’ task-specific goal orientation (response pattern adopted for a specific task). One hundred and three participants performed an air traffic control task and their task-specific goal orientation was measured prior to each of a total of thirty trials. Results revealed an effect of task practice such that individuals’ task-specific learning orientation decreased over time while their task-specific prove orientation increased over time. The results also showed that individuals’ personality can influence their task-specific goal orientation and further, that this relationship can be mediated by global goal orientation. Specifically, the positive relationship between openness to experience and task-specific prove orientation was mediated by global prove orientation. Similarly, the positive relationship between neuroticism and task-specific avoid orientation was mediated by global avoid orientation. Theoretical and practical implications of these findings are considered.

Language against the odds, or rather not:the weak central coherence hypothesis and language

EV is a child with a talent for learning language combined with Asperger syndrome. EV’s talent is evident in the unusual circumstances of her acquisition of both her first (Bulgarian) and second (German) languages and the unique patterns of both receptive and expressive language (in both the L1 and L2), in which she shows subtle dissociations in competence and performance consistent with an uneven cognitive profile of skills and abilities. We argue that this case provides support for theories of language learning and usage that require more general underlying cognitive mechanisms and skills. One such account, the Weak Central Coherence (WCC) hypothesis of autism, provides a plausible framework for the interpretation of the simultaneous co-occurrence of EV’s particular pattern of cognitive strengths and weaknesses. Furthermore, we show that specific features of the uneven cognitive profile of Asperger syndrome can help explain the observed language talent displayed by EV. Thus, rather than demonstrating a case where language learning takes place despite the presence of deficits, EV’s case illustrates how a pattern of strengths within this profile can specifically promote language learning.

The manufacture and utilisation of architectural terracotta and faience.

The revival of terracotta and faience in British architecture was widespread, dramatic in its results and, for two decades, the subject of intense debate. However the materials have been frequently denigrated and more generally disregarded by both architects and historians. This study sets out to record and explain the rise and fall of interest in terracotta and faience, the extent and nature of the industry and the range of architectural usage in the Victorian, Edwardian and inter-war periods. The first two chapters record the faltering use of terracotta as an 'artificial stone', until the material gained its own identity, largely through the appreciation of Italian architecture. In the mid-Victorian period, terracotta will be seen to have become symbolic of the philosophy of the Victoria and Albert Museum and its Art School in attempting to reform both architecture and the decorative arts. The adoption of terracotta was furthered as much by industrial as aesthetic factors; three chapters examine how the exploitation of coal-measure clays, developments in the processes of manufacture, the changing motivation of industrialists and differing economics of production served to promote and then to hinder expansion and adaptation. The practical values of economy, durability and fire-resistance and the aesthetic potential, seen in terms of colour and decorative and sculptural modelling, became inter-related in the work of the architects who made extensive use of architectural ceramics. A correlation emerges between the free Gothic style, exemplified by the designs of Alfred Waterhouse and the use of red terracotta supplied from Ruabon, and between the eclectic Renaissance style and a buff material produced by different manufacturers.These patterns were modified as a result of the adoption of faience for facing external walls as well as interiors, and because of the new architectural requirements and tastes of the twentieth century. The general timidity in exploiting the scope for polychromatic decoration and the increasing opposition to architectural ceramics is contrasted with the most successful schemes produced for cinemas, chain-stores and factories. In the last chapter, those undertaken by the Hathern Station Brick and Terracotta Company between 1896 and 1939 are used as a case study; they confirm that manufacturers, architects and clients were all committed to creating a modern and yet decorative architecture, appropriate for new building types and that would appeal to and be comprehensible to the public.

A new dynamic framework for managing ERP development and enterprise strategy

The enterprise management (EM) approach provides a holistic view of organizations and their related information systems. In order to align information technology (IT) innovation with global markets and volatile virtualization, traditional firms are seeking to reconstruct their enterprise structures alongside repositioning strategy and establish new information system (IS) architectures to transform from single autonomous entities into more open enterprises supported by new Enterprise Resource Planning (ERP) systems. This chapter shows how ERP engage-abilities cater to three distinctive EM patterns and resultant strategies. The purpose is to examine the presumptions and importance of combing ERP and inter-firm relations relying on the virtual value chain concept. From a review of the literature on ERP development and enterprise strategy, exploratory inductive research studies in Zoomlion and Lanye have been conducted. In addition, the authors propose a dynamic conceptual framework to demonstrate the adoption and governance of ERP in the three enterprise management forms and points to a new architectural type (ERPIII) for operating in the virtual enterprise paradigm. © 2012, IGI Global.

Was it good for them? Reflections on the use of MENTOR and changes in course design using general performance measures

This paper considers the use of general performance measures in evaluating specific planning and design decisions in higher education and reflects on the students' learning process. Specifically, it concerns the use of the MENTOR multimedia computer aided learning package for helping students learn about OR as part of a general business degree. It includes the transfer of responsibility for a learning module to a new staff member and a change from a single tutor to a system involving multiple tutors. Student satisfaction measures, learning outcome measures and MENTOR usage patterns are examined in monitoring the effects of the changes in course delivery. The results raise some questions about the effectiveness of general performance measures in supporting specific decisions relating to course design and planning.