bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Significance of, and Gene and MicroRNA Expression Signatures Associated With, CEBPA Mutations in Cytogenetically Normal Acute Myeloid Leukemia With High-Risk Molecular Features: A Cancer and Leukemia Group B Study
Authors: Marcucci Guido , Maharry Kati , Radmacher Michael D. , Mrózek Krzysztof , Vukosavljevic Tamara , Paschka Peter , Whitman Susan P. , Langer Christian , Baldus Claudia D. , Liu Chang-Gong , Ruppert Amy S. , Powell Bayard L. , Carroll Andrew J. , Caligiuri Michael A. , Kolitz Jonathan E. , Larson Richard A. , Bloomfield Clara D.
Published: September 2008

Purpose

To evaluate the prognostic significance of CEBPA mutations in the context of established molecular markers in cytogenetically normal (CN) acute myeloid leukemia (AML) and gain biologic insights into leukemogenesis of the CN-AML molecular high-risk subset (FLT3 internal tandem duplication [ITD] positive and/or NPM1 wild type) that has a significantly higher incidence of CEBPA mutations than the molecular low-risk subset (FLT3-ITD negative and NPM1 mutated).

Patients and Methods

One hundred seventy-five adults age less than 60 years with untreated primary CN-AML were screened before treatment for CEBPA, FLT3, MLL, WT1, and NPM1 mutations and BAALC and ERG expression levels. Gene and microRNA (miRNA) expression profiles were obtained for the CN-AML molecular high-risk patients.

Results

CEBPA mutations predicted better event-free (P = .007), disease-free (P = .014), and overall survival (P < .001) independently of other molecular and clinical prognosticators. Among patients with CEBPA mutations, 91% were in the CN-AML molecular high-risk group. Within this group, CEBPA mutations predicted better event-free (P < .001), disease-free (P = .004), and overall survival (P = .009) independently of other molecular and clinical characteristics and were associated with unique gene and miRNA expression profiles. The major features of these profiles were upregulation of genes (eg, GATA1, ZFPM1, EPOR, and GFI1B) and miRNAs (ie, the miR-181 family) involved in erythroid differentiation and downregulation of homeobox genes.

Conclusion

Pretreatment testing for CEBPA mutations identifies CN-AML patients with different outcomes, particularly in the molecular high-risk group, thus improving molecular risk-based classification of this large cytogenetic subset of AML. The gene and miRNA expression profiling provided insights into leukemogenesis of the CN-AML molecular high-risk group, indicating that CEBPA mutations are associated with partial erythroid differentiation.
Late Congestive Heart Failure After Hematopoietic Cell Transplantation
Authors: Armenian Saro H. , Sun Can-Lan , Francisco Liton , Steinberger Julia , Kurian Seira , Wong F. Lennie , Sharp Jon , Sposto Richard , Forman Stephen J. , Bhatia Smita
Published: September 2008

Purpose

To examine the independent roles of pre–hematopoietic cell transplantation (HCT) therapeutic exposures, transplantation-related conditioning, and comorbidities (pre- and post-HCT) in the development of late congestive heart failure (CHF) after HCT.

Methods

This was a nested case-control design. Individuals with late CHF (diagnosed ≥ 1 year after HCT) were identified from a cohort of 2,938 1+ year survivors who underwent transplantation at City of Hope National Medical Center, Duarte, CA. This cohort formed the sampling frame for selecting controls (without CHF) matched for age and year of HCT, donor source (allogeneic v autologous), and length of follow-up.

Results

Sixty patients with late CHF were identified; median age at HCT was 45.3 years (range, 16.6 to 68.6 years); median time to CHF was 3.0 years (range, 1.03 to 18.9 years); 68% received autologous HCT. Median ejection fraction was 36.9% (range, 15% to 53%). Compared with matched controls (n = 166), patients with late CHF received more cycles of pre-HCT chemotherapy (8.6 v 4.9 cycles; P < .01), had greater body mass index at HCT (28.4 v 26.2 kg/m2; P = .01), greater lifetime anthracycline exposure (285.3 v 175.6 mg/m2; P < .01), and were more likely to have multiple chronic comorbidities (30.0% v 13.9%; P < .01). Multivariable analysis revealed number of pre-HCT chemotherapy cycles (odds ratio [OR] = 1.2; P < .01), anthracycline dose ≥ 250 mg/m2 (OR = 3.2; P = .05), and two or more chronic comorbidities (OR = 4.3; P = .01) to be independently associated with late CHF.

Conclusion

Pre-HCT exposure to anthracyclines and presence of comorbidities are primarily responsible for the risk associated with late CHF after HCT. Conditioning-related therapeutic exposure does not contribute significantly to the risk. These results form the basis for identifying high-risk individuals for targeted surveillance, as well as developing preventive strategies in the form of aggressive management of comorbidities.
Association of the Timing of Puberty with a Chromosome 2 Locus
Authors: Wehkalampi Karoliina , Widén Elisabeth , Laine Tiina , Palotie Aarno , Dunkel Leo
Published: September 2008

Context: Twin studies indicate that the timing of pubertal onset is under strong genetic control. However, genes controlling pubertal timing in the general population have not yet been identified.

Objective: To facilitate the identification of genes influencing the timing of pubertal growth and maturation, we conducted linkage mapping of constitutional delay of growth and puberty (CDGP), an extreme variant of normal pubertal timing, in extended families.

Participants and Methods: Fifty-two families multiply affected with CDGP were genotyped with 383 multiallelic markers. CDGP was defined based on growth charts (the age at onset of growth spurt, peak height velocity, or attaining adult height taking place at least 1.5 sd later than average). Chromosomal regions cosegregating with CDGP were identified with parametric affected-only linkage analysis using CDGP as a dichotomized trait.

Results: The genome-wide scan detected linkage of CDGP to a region on chromosome 2p13-2q13. The two-point heterogeneity LOD (HLOD) score was 1.62 (α = 0.27), and the corresponding multipoint HLOD was 2.54 (α = 0.31). Fine-mapping the region at 1 cM resolution increased the multipoint HLOD score to 4.44 (α = 0.41). The linkage became weaker if family members diagnosed with CDGP without growth data were also included in the analyses.

Conclusions: The pericentromeric region of chromosome 2 harbors a gene predisposing to pubertal delay in multiply affected pedigrees. Our data suggest that this locus may be a component of the internal clock controlling the timing of the onset of puberty.
Study on predictive functional control of an expansion valve for controlling the evaporator superheat
Authors: Changenet C , Charvet J N , Géhin D , Sicard F , Charmel B
Published: September 2008

A new method is proposed to control the evaporator superheat with an electronic expansion valve. The conventional proportional-integral-derivative (PID) control with invariable parameters cannot show good performance because of the variation of refrigeration unit parameters under disturbances. To solve this problem, this paper presents a method for the use of predictive functional controllers (PFCs) on superheat of an evaporator. This method is based on a physical model of the appliance studied to allow calculation of parameters needed for the use of PFCs. The control system created is incorporated into an industrial programmable logic controller and used for experiments on a refrigerating machine containing a shell and tubes evaporator with R410A as refrigerant fluid. The comparison between the two types of controller, i.e. PID and PFC, indicates that superheat may be more efficiently controlled by using the latter type of controller: the setting value is only slightly exceeded, there are only small oscillations of measured superheat, and the energy efficiency of the refrigeration unit may be improved.
Increasing appropriateness of hospital admissions in the Emilia-Romagna region of Italy
Authors: Louis Daniel , Taroni Francesco , Melotti Rita , Rabinowitz Carol , Vizioli Maria , Fiorini Monica , Gonnella Joseph
Published: September 2008

Objectives:

The Emilia-Romagna region of Italy has reduced the number of available hospital beds and introduced financial incentives to curb hospital use. The goal of this study was to assess the impact of these policies on changes over time in the number of acute hospital admissions classified in diagnosis related groups (DRGs) that could be treated safely and effectively in alternative, less costly settings.

Methods:

The assessment of the appropriate site of care was based on analysis of hospital discharge data for all hospitals for the selected diagnosis related groups in the Emilia-Romagna region for 2001 to 2005. The necessity for acute hospital admission was based on the severity of a patient's principal diagnosis, co-morbid diseases and, for surgical admissions, procedure performed.

Results:

From 2001 to 2005, potentially inappropriate medical admissions of more than one day decreased from 20,076 to 11,580, a 42% decrease. Inappropriate admissions decreased in both public and private hospitals but there remained a higher rate of inappropriate admissions to private hospitals. Potentially inappropriate medical admissions accounted for 128,319 bed-days in 2001 and 68,968 bed-days in 2005, a reduction of 59,351 bed-days. Potentially inappropriate surgical admissions decreased from 7383 in 2001 to 4349 in 2005, a 41% decrease. Bed-days consumed by inappropriate surgical admissions decreased from 23,181 in 2001 to 13,660 in 2005.

Conclusions:

The Emilia-Romagna region has succeeded in reducing the use of acute hospital beds for patients in selected diagnosis related groups. However, there are still substantial numbers of admissions that could potentially be treated in less costly settings.
What leads to better health care innovation? Arguments for an integrated policy-oriented research agenda
Authors: Lehoux Pascale , Williams-Jones Bryn , Miller Fiona , Urbach David , Tailliez Stephanie
Published: September 2008

This essay is based on the recognition that the current ‘downstream’ health services research and policy approach to innovation misses the mark on one crucial point. It has not addressed how to promote the design of innovations that are likely to be more valuable than others. Re-visiting the ways in which health services research could inform innovation processes, this paper suggests that three attributes make innovations especially compelling from a health care system perspective: relevance; usability; and sustainability. These could be used as a starting point for outlining a policy-oriented research agenda that could bridge upstream design processes, and downstream needs and priorities. Given the pace at which innovations come about and the complexity of health care systems, we believe that both research and policy should be able to contribute significantly to the shaping of socially valuable technological change in health care. Recognizing that such a long-term goal cannot be reached through a linear, rationalistic process, our paper offers preliminary arguments to start to reconcile the health policy and innovation agendas.
Designing and implementing behaviour change interventions to improve population health
Authors: Michie Susan
Published: September 2008

Improved population health depends on changing behaviour: of those who are healthy (e.g. stopping smoking), those who are ill (e.g. adhering to health advice) and those delivering health care. To design more effective behaviour change interventions, we need more investment in developing the scientific methods for studying behaviour change. Behavioural science is relevant to all phases of the process of implementing evidence-based health care: developing evidence through primary studies, synthesizing the findings in systematic reviews, translating evidence into guidelines and practice recommendations, and implementing these in practice. ‘Behaviour change: Implementation and Health’, the last research programme to be funded within the MRC HSRC, aimed to develop innovative ways of applying theories and techniques of behaviour change to understand and improve the implementation of evidence-based practice, as a key step to improving health. It focused on four areas of study that apply behaviour change theory: • defining and developing a taxonomy of behaviour change techniques to allow replication of studies and the possibility of accumulating evidence; • conducting systematic reviews, by categorizing and synthesizing interventions on the basis of behaviour change theory; • investigating the process by which evidence is translated into guideline recommendations for practice; • developing a theoretical framework to apply to understanding implementation problems and designing interventions.

This work will contribute to advancing the science of behaviour change by providing tools for conceptualizing and defining intervention content, and linking techniques of behaviour change to their theoretical base.
Decision analysis for resource allocation in health care
Authors: Griffin Susan , Claxton Karl , Sculpher Mark
Published: September 2008

This paper addresses the use of economic evaluation to inform resource allocation decisions within health care systems about which interventions to reimburse and whether additional research should be funded. A social decision-making view of economic evaluation, that is to maximize health gains subject to an exogenous budget constraint, is adopted.

A brief overview of the components of an economic evaluation is presented. Particular attention is paid to how uncertainty is inherent to decisions about resource allocation, the consequences of that uncertainty and how it can be incorporated informatively into economic evaluation. A Bayesian approach to uncertainty is used as it meets the needs of social decision-making, allowing analysts to quantify the probability that an intervention is cost-effective given the available evidence and to quantify the expected value of further research.

The discussion covers methods to represent parameter and structural uncertainty and considers the role of formal elicitation of expert judgements. The association between decisions to approve interventions for reimbursement and decisions about future research funding, and how value of information analysis can be used to formalize this link, is explained.

Recent developments in the UK highlight the evolving policy environment for economic evaluation, such as the Cooksey report on the funding of UK health research, the review of the Pharmaceutical Price Regulation Scheme by the Office of Fair Trading and the update of the methodological guidelines issued by the National Institute for Health and Clinical Excellence. The paper concludes by describing ongoing methodological work designed to meet the challenges of undertaking decision analysis for resource allocation in health care.
Multiparameter evidence synthesis in epidemiology and medical decision-making
Authors: Ades A E , Welton Nicky J , Caldwell Deborah , Price Malcolm , Goubar Aicha , Lu Guobing
Published: September 2008

Meta-analysis has been well-established for many years, but has been largely confined to pooling evidence on pair-wise contrasts. Broader forms of synthesis have also been described, apparently re-invented in disparate fields, each time taking different computational approaches. The potential value of Bayesian estimation of a joint posterior parameter distribution and simultaneously sampling from it for decision analysis has also been appreciated. However, applications have been relatively few in number, sometimes stylized, and presented mainly to a statistical methods audience. As a result, the potential for multiparameter evidence synthesis in both epidemiology and health technology assessment has remained largely unrecognized. The advent of flexible software for Bayesian Markov chain Monte Carlo in the shape of WinBUGS has the made these earlier strands of work more widely available. Researchers can now carry out synthesis at a realistic level of complexity. The Bristol programme has not only contributed to a growing body of literature on how to synthesize different evidence structures, but also on how to check the consistency of multiple information sources and how to use the resulting models to prioritize future research.
Investigating Choice Experiments for Preferences of Older People (ICEPOP): Evaluative spaces in health economics
Authors: Coast Joanna , Flynn Terry , Sutton Eileen , Al-Janabi Hareth , Vosper Jane , Lavender Sarita , Louviere Jordan , Peters Tim
Published: September 2008

This paper deals with three concerns about the evaluative framework that is currently dominant within health economics. These concerns are: that the evaluative framework is concerned entirely with health; that the evaluative framework has an individualistic focus on patients alone; and that the methods used to estimate ‘health’ within the current evaluative framework could be improved both in terms of the generation of descriptive systems and in using valuation methods that rely less on people's ability to express their preferences on a cardinal scale. In exploring these issues the Investigating Choice Experiments for Preferences of Older People (ICEPOP) programme has explicitly focused on both the topic of older people and the methods of discrete choice experiments. A capability index has been developed and attributes for an economic measure of end-of-life care are currently being generated, providing the possibility of extending the evaluative framework beyond health alone. A measure of carer's experience and a framework for extending measurement in end-of-life care to loved ones are both also in development, thus extending the evaluative framework beyond the patient alone. Rigorous qualitative methods employing an iterative approach have been developed for use in constructing attributes, and best-worst scaling has been utilized to reduce task complexity and provide insights into heterogeneity. There are a number of avenues for further research in all these areas, but in particular there is need for greater attention to be paid to the theory underlying the evaluative framework within health economics.
The impact of income on private patients’ access to GP services in Ireland
Authors: Nolan Anne
Published: September 2008

Objectives:

To examine the extent to which proximity to the income threshold for free GP care results in significant differences in GP visiting. Approximately 30% of the Irish population receives free GP care (medical card patients), while the remaining 70% pays in full (private patients). Medical card eligibility exerts a significant influence on GP visiting, but how do GP visiting rates differ among private patients on differing incomes, and has the differential in visiting among private patients changed over time?

Methods:

Using micro-data from three nationally representative surveys of the Irish population undertaken in 1987, 1995 and 2001, multivariate models of GP utilization are estimated.

Results:

There is little evidence that proximity to the income threshold results in significant differences in GP visiting. The most significant difference is between medical card and private patients, rather than between private patients on differing incomes. There is also little evidence that the differential in GP visiting between private patients on different incomes changed over time.

Conclusions:

While recent commentary has focused on the plight of individuals just above the income threshold for free GP care, these results suggest that the key difference in GP visiting is between those with, and without, eligibility for free care. If private patients are prevented from accessing GP care due to cost, this is as much an issue for those at the top of the income distribution as for those at the bottom.
Moving specialist care into the community: An initial evaluation
Authors: Sibbald Bonnie , Pickard Susan , McLeod Hugh , Reeves David , Mead Nicola , Gemmell Islay , Coast Joanna , Roland Martin , Leese Brenda
Published: September 2008

Objectives:

To assess the likely impact on patients and local health economies of shifting specialist care from hospitals to the community in 30 demonstration sites in England.

Methods:

The evaluation comprised: interviews with service providers at 30 sites, supplemented by interviews with commissioners, GPs and hospital doctors at 12 sites; economic case studies in six sites; and patient surveys at 30 sites plus at nine conventional outpatient services. Outcomes comprised: staff views of service organization and development, impact on primary and secondary care, and benefits for patients; cost per consultation and cost per patient in new services compared to estimates of the price of services if undertaken by hospitals; patients’ views of waiting time, access, quality (technical and interpersonal), coordination and satisfaction.

Results:

New services required high initial investment in staff, premises and equipment, and the support of hospital consultants. Most new services were added to existing hospital services so expanded capacity. Patient reported waiting times (6.7 versus 10.1 weeks; p = 0.001); technical quality of care (96.2 versus 94.5; p < 0.001), overall satisfaction (88.2 versus 85.4; p = 0.04); and access (72.2 versus 65.8; p = 0.001) were significantly better for new compared to conventional services but there was no significant difference in coordination or interpersonal quality of care. Some service providers expressed concerns about service quality. New services dealt with less complex conditions and undercut the price tariff applied to hospitals thus providing a cost saving to commissioners. There was some concern that expansion of new services might destabilize hospitals.

Conclusions:

Moving specialist care into the community can improve patient access, particularly when new services are added to existing hospital services. Wider impacts on health care quality, capacity and cost merit closer scrutiny before rollout.
Health care professionals’ views of implementing a policy of open disclosure of errors
Authors: Sorensen Ros , Iedema Rick , Piper Donella , Manias Elizabeth , Williams Allison , Tuckett Anthony
Published: September 2008

Objectives:

To understand the views of doctors, nurses, allied health professionals and health managers of open disclosure of medical errors.

Methods:

Semi-structured interviews were conducted with 131 health professionals to understand their experiences of implementing open disclosure in 21 providers in Australia.

Results:

Health professionals are positive about open disclosure and are applying the model to patient- clinician communication encounters more generally. Workforce and systems competencies enable clinicians and health service managers to implement open disclosure principles and practices, although a propensity to hide errors, wavering commitment and to exacerbate the problem inhibits implementation as policy intends. The gap between policy objectives and their implementation limits the benefits to health professionals.

Conclusion:

Health services must develop organizing capabilities if open disclosure is to be implemented as intended. Activities should identify and address factors that impede implementation and enable workforce and system competencies to develop. These activities will allow health services to adapt central open disclosure policy to local conditions and to embed its principles and practices organization-wide.
The impact of an educational pamphlet on knowledge and anxiety in women with preeclampsia
Authors: Sauvé Nadine , Powrie Raymond O , Larson Lucia , Phipps Maureen G , Weitzen Sherry , Fitzpatrick Donna , Rosene-Montella Karen
Published: September 2008

Objective:

This study was undertaken to evaluate whether or not an educational pamphlet could improve knowledge without increasing anxiety in women with preeclampsia.

Methods:

One hundred women recruited from an inpatient setting with suspected or proven preeclampsia were asked to answer a questionnaire assessing demographics, knowledge (primary outcome), anxiety and satisfaction (secondary outcomes) after being randomized to an intervention group (who received a pamphlet) or a control group (who did not received a pamphlet). The pamphlet and questionnaire, both designed by a multidisciplinary team, were read and answered at the same time.

Results:

Baseline and demographic characteristics were similar between the two groups. Knowledge about the symptoms of pre-eclampsia was excellent in both groups (61% to 100% correct answers). Women in both groups were well aware that preeclampsia in the past ( P = 0.22) and a family history of preeclampsia ( P = 0.57) were risk factors. There was a significant difference in knowledge about the risk of some fetal complications, including death (90% versus 39%, P < 0.01) and all maternal complications ( P < 0.05) favouring the intervention group. Despite increased knowledge about preeclampsia and its risks, anxiety was not greater in the intervention group. Overall, there was a trend towards less knowledge in vulnerable subgroups (non-white, low income and schooling levels), but the improvement of knowledge with the pamphlet was equivalent. Baseline anxiety was higher in the vulnerable groups, but was generally not increased by the pamphlet.

Conclusion:

An educational pamphlet for women with suspected preeclampsia was able to increase knowledge without increasing anxiety.
Maternal mortality in the developing world: why do mothers really die?
Authors: Lewis Gwyneth
Published: September 2008

Every year some eight million women suffer preventable or remediable pregnancy-related complications and over half a million will die unnecessarily. Most of these deaths could be averted at little or no extra cost, even where resources are limited, but in order to take action, and develop and implement changes to maternity services to save mothers and newborns lives, a change in cultural attitudes and political will, as well as improvements in the provision of health and social care, is required.

Further, to aid programme planners, more in-depth information than that which may already be available through national statistics on maternal mortality rates or death certificate data is urgently needed. What is required is an in-depth understanding of the clinical, social, cultural or any other underlying factors which lead to mothers' deaths. Such information can be obtained by using any of the five methodologies outlined in the World Health Organizations programme and philosophy for maternal death or disability reviews, ‘Beyond the Numbers’, briefly described here and which are now being introduced in a number of countries around the world.
Maternal mortality in the developed world: lessons from the UK confidential enquiry
Authors: de Swiet Michael
Published: September 2008

The UK confidential maternal mortality enquiry shows that not only has maternal mortality decreased since 1952, the year of the first enquiry, but also the pattern of maternal mortality has changed markedly. Major surgical causes of death, such as post-partum haemorrhage and ruptured uterus, are no longer as important as medical causes such as heart disease. The ‘Top Ten’ recommendations in the current report for the years 2003–2005 emphasise the need for health care practitioners to be aware of the risks that medical conditions, both pre-existing and those arising de novo in pregnancy, impose on the expectant and newly delivered mother. Training and further education programmes should emphasise the importance of medical problems in pregnancy without omitting the knowledge and skills in basic obstetrics that have made such an impact on maternal mortality in the past.
A bioinformatics tool for linking gene expression profiling results with public databases of microRNA target predictions
Authors: Creighton Chad J. , Nagaraja Ankur K. , Hanash Samir M. , Matzuk Martin M. , Gunaratne Preethi H.
Published: September 2008

MicroRNAs are short (∼22 nucleotides) noncoding RNAs that regulate the stability and translation of mRNA targets. A number of computational algorithms have been developed to help predict which microRNAs are likely to regulate which genes. Gene expression profiling of biological systems where microRNAs might be active can yield hundreds of differentially expressed genes. The commonly used public microRNA target prediction databases facilitate gene-by-gene searches. However, integration of microRNA–mRNA target predictions with gene expression data on a large scale using these databases is currently cumbersome and time consuming for many researchers. We have developed a desktop software application which, for a given target prediction database, retrieves all microRNA:mRNA functional pairs represented by an experimentally derived set of genes. Furthermore, for each microRNA, the software computes an enrichment statistic for overrepresentation of predicted targets within the gene set, which could help to implicate roles for specific microRNAs and microRNA-regulated genes in the system under study. Currently, the software supports searching of results from PicTar, TargetScan, and miRanda algorithms. In addition, the software can accept any user-defined set of gene-to-class associations for searching, which can include the results of other target prediction algorithms, as well as gene annotation or gene-to-pathway associations. A search (using our software) of genes transcriptionally regulated in vitro by estrogen in breast cancer uncovered numerous targeting associations for specific microRNAs—above what could be observed in randomly generated gene lists—suggesting a role for microRNAs in mediating the estrogen response. The software and Excel VBA source code are freely available at http://sigterms.sourceforge.net.
Physician, affective, and cognitive variables differentially predict initiation versus maintenance PSA screening profiles in diverse groups of men
Authors: Consedine Nathan S. , Christie Michael A. , Neugut Alfred I.
Published: September 2008

Objectives To evaluate the relevance of demographic, physician, and psychological characteristics to PSA screening in ethnic subpopulations and ascertain whether the same characteristics distinguish men who have never had a PSA from those who screen infrequently and those who screen yearly (adhere).

Design and methods Stratified cluster‐sampling was used to recruit 533 men (45–70 years) from four ethnic groups: African‐American; European‐American; immigrant Jamaican; and immigrant men from Trinidad and Tobago. Men provided demographic and structural (insurance, regular physician, annual exam, and physician recommendation), cognitive (risk and efficacy perceptions, knowledge), and emotional variables (cancer worry and embarrassment), and reported on PSA screening history. Multinomial logistic regression used these variables to predict three screening classifications (never screened, partially adherent, and adherent).

Results Multinomial logistic regression showed that minority men were less likely to report either never screening or yearly screening, while younger men were more likely. Lack of a regular physician (OR=2.87, 95% CI 1.39–5.84), an annual exam (OR=1.73, 95% CI 0.91–3.28), and low recommendation (OR=3.76, 95% CI 2.13–6.66) were associated with being categorized as a never (vs. partially adherent) screener, but only annual exam (OR=0.26, 95% CI 0.10–0.63) was associated with yearly screening. Lower cancer worry was marginally associated with never screening (OR=0.59, 95% CI 0.38–1.04), while knowledge was associated with screening yearly over time (OR=0.46, 95% CI 0.28–0.77).

Conclusions Demographic, physician, and psychological variables are differentially associated with never, less than yearly, and yearly screening classifications. Minority men were unlikely to have never screened, but were also less likely to screen yearly. Physician variables were associated with the difference between not screening and partially adherent, but not between partially adherent and yearly screening suggesting that the role of physicians in PSA behaviour over time would benefit from further study.
Five factor model personality factors moderated the effects of an intervention to enhance chronic disease management self‐efficacy
Authors: Franks Peter , Chapman Benjamin , Duberstein Paul , Jerant Anthony
Published: September 2008

Objectives. Peer led interventions can enhance patient self‐efficacy for managing chronic illnesses, but little is known regarding the moderators or duration of their effects. We hypothesized Homing in on Health (HIOH), a variant of the Chronic Disease Self‐Management Program, would be most effective in patients high in neuroticism and low in extraversion, openness, agreeableness, and/or conscientiousness.

Design. Analysis of data from subjects (N = 415) enrolled in an ongoing randomized controlled trial.

Methods. Regression analyses were conducted to explore whether Five Factor Model (FFM) personality factors moderated the effects of HIOH, delivered in subjects' homes or via telephone, on disease management self‐efficacy. Data were collected at 6 time points over the course of 1 year.

Results. Compared with control and telephone HIOH, home HIOH significantly increased self‐efficacy, an effect peaking at 6 weeks and fully attenuating by 1year. Moderation analyses revealed the benefit was confined to patients higher in neuroticism and/or lower in conscientiousness, agreeableness, and extraversion.

Conclusions. A peer led intervention to enhance disease management self‐efficacy had only short‐term effects, and FFM personality factors moderated those effects. Measuring personality factors in chronically ill individuals may facilitate targeting of self‐management interventions to those most likely to respond.
Predicting breakfast consumption: An application of the theory of planned behaviour and the investigation of past behaviour and executive function
Authors: Wong Cara L. , Mullan Barbara A.
Published: September 2008

Objectives. The objective of the current study is to examine the determinants of breakfast consumption with the application of the Theory of Planned Behaviour (TPB; 1991) and investigate the additional variables of past behaviour and executive function.

Design. A prospective 1‐week study investigating the predictive ability of TPB variables, past behaviour and executive function was utilized.

Methods. Ninety‐six participants were administered two measures of executive function (response inhibition and planning) and completed self‐report questionnaires regarding their attitudes, subjective norms, perceived control, intentions and past behaviour of breakfast consumption. One week later, participants returned a follow‐up questionnaire on their behaviour.

Results. The result of the study showed that the TPB significantly predicted intentions and prospective behaviour of breakfast consumption, however, past behaviour was found to be the strongest predictor of future behaviour. Considering executive function, response inhibition was not found to predict behaviour, however, planning ability explained unique variance in behaviour and moderated the association between intention and behaviour.

Conclusions. The findings support the use of the TPB in explaining breakfast eating habits, and suggest that executive function of planning may be somewhat useful to predict this behaviour. The significance of past behaviour also suggests that breakfast consumption may commonly be a stable, habitual behaviour that may undermine the need for self‐regulation. Implications for creating behavioural‐change interventions are discussed.
Laboratory evaluation of kidney function in the elderly1
Authors: Holdt Birgit , Schuff-Werner Peter
Published: September 2008

Demographic changes and the increasing proportion of elderly among the overall population call for consideration of the morphology and function of the ageing kidney. Its hallmarks include progressive loss of kidney function reserve and potential for compensation. Differentiation from true kidney disease and/or injury is important, since early diagnosis allows for treatment that may delay progression of renal disease in the elderly.

The glomerular filtration rate (GFR) is the recommended laboratory parameter to describe glomerular function of the kidney and hence to distinguish the different stages of chronic renal diseases. Current discussions focus on estimated GFR formulas based on endogenous substances (creatinine and cystatin C). Unfortunately, these estimated GFR formulas were not specifically developed for the aged population and reference ranges for a normal renal function are not defined beyond the age of 70 years. There are inconsistencies between data sets of formulas depending on age and disease. No methods have been validated for determination of glomerular and tubular renal function in the elderly.

Until the validation of estimated GFR formulas or new biomarkers, one relies on formulas tested and additional renal and non-renal laboratory parameters. These should be applied according to recent physical findings. Age, disease and ongoing therapy should influence the selection of a formula with the least deviation from the gold standard (exogenous clearance). The consistent use of standardised methods and calibrators will advance the estimation of renal function in the elderly.

The initial assessment of the ageing kidney remains a challenge with the risk of both over- and underestimating kidney function. Follow-up investigation is essential to monitor changes from individual baseline kidney function.

The main goal of current and future studies will be the individual assessment of kidney function in the elderly considering its functional reserve.
Comparative evaluation of different D-dimer assays for exclusion of venous thromboembolism in a clinical routine setting1
Authors: Roggenbuck Lennart , Dörner Klaus
Published: September 2008

The aim of our prospective study on 246 consecutive outpatients with suspected acute venous thromboembolism (VTE) was to evaluate the actual performance of four D-dimer assays (D-dimer plus, Stratus CS, Innovance, Siemens Medical Solutions Diagnostics, and Tina-quant D-dimer, Roche Diagnostics) for exclusion of VTE. Analysis was initiated after false negative results in three patients with proven VTE were observed in routine diagnostics.

Diagnostic sensitivity, specificity, negative and positive predictive values of the D-dimer tests were calculated based on recommended cut-off levels and on upper limits of corresponding 95% confidence intervals (95% CI). VTE was confirmed in 46 patients (18.7%) by imaging techniques. The D-dimer plus assay yielded seven false negative results (nine considering 95% CI) in 46 patients. A sensitivity of 84.8% and 80.4% and a negative predictive value of 93.8% and 93.0%, respectively, was achieved. In contrast, the alternative tests showed no false negative results (sensitivity and negative predictive value 100%), and a higher D-dimer result to cut-off ratio.

Detection of performance deficiencies of established diagnostic assays requires close cooperation with the clinician and further evaluation by the medical laboratory in accordance with the requirements of DIN EN ISO 15189.
Natural killer cells and natural killer T cells in patients with renal transplantation1
Authors: Hoppe Anett , Kamprad Manja , Wegmann Claudia , Wötzel Michael , Hauss Johann , Emmrich Frank , Fangmann Josef , Sack Ulrich
Published: September 2008

Notwithstanding high clinical standards, renal transplantation, as the established procedure for treating terminal renal failure, involves the risk of numerous complications, especially in the postoperative period. Rejection episodes and bacterial, viral as well as fungal infections are of particular relevance. Frequently their timely clinical as well as laboratory identification and the resulting therapeutic consequences are too imprecise. This paper describes a practice-oriented concept for immunological monitoring within 28 days of observation following transplantation, including natural killer cells (NK) and natural killer T cells (NKT cells). This monitoring process focuses on flow cytometric identification of the functional markers NKp30, NKp44, NKp46, CD16 and CXCR3 on NK and NKT cells. Both cell populations were influenced by the therapy. While there was hardly any difference between living and cadaver donors and while no significant differences were found between the immunosuppressants, NKT cell findings in particular appear to make a diagnostic use of these cells possible while the graft is being monitored. The development of these cells following renal transplantation shows the changes typical under standard immunosuppression and permits the identification of postoperative complications.
Involvement of the Limbic Basal Ganglia in Ethanol Withdrawal Convulsivity in Mice Is Influenced by a Chromosome 4 Locus
Authors: Chen Gang , Kozell Laura B. , Hitzemann Robert , Buck Kari J.
Published: September 2008

Physiological dependence and associated withdrawal episodes are thought to constitute a motivational force that sustains ethanol (alcohol) use/abuse and may contribute to relapse in alcoholics. Although no animal model duplicates alcoholism, models for specific factors, like the withdrawal syndrome, are useful for identifying potential genetic and neural determinants of liability in humans. We generated congenic mice that confirm a quantitative trait locus (QTL) on chromosome 4 with a large effect on predisposition to alcohol withdrawal. Using c-Fos expression as a high-resolution marker of neuronal activation, congenic mice demonstrated significantly less neuronal activity associated with ethanol withdrawal than background strain mice in the substantia nigra pars reticulata (SNr), subthalamic nucleus (STN), rostromedial lateral globus pallidus, and ventral pallidum. Notably, neuronal activation in subregions of the basal ganglia associated with limbic function was more intense than in subregions associated with sensorimotor function. Bilateral lesions of caudolateral SNr attenuated withdrawal severity after acute and repeated ethanol exposures, whereas rostrolateral SNr and STN lesions did not reduce ethanol withdrawal severity. Caudolateral SNr lesions did not affect pentylenetetrazol-enhanced convulsions. Our results suggest that this QTL impacts ethanol withdrawal via basal ganglia circuitry associated with limbic function and that the caudolateral SNr plays a critical role. These are the first analyses to elucidate circuitry by which a confirmed addiction-relevant QTL influences behavior. This mouse QTL is syntenic with human chromosome 9p. Given the growing body of evidence that a gene(s) on chromosome 9p influences alcoholism, our results can facilitate human research on alcohol dependence and withdrawal.
The Genomic Response of the Retinal Pigment Epithelium to Light Damage and Retinal Detachment
Authors: Rattner Amir , Toulabi Leila , Williams John , Yu Huimin , Nathans Jeremy
Published: September 2008

The retinal pigment epithelium (RPE) plays an essential role in maintaining the health of the retina. The RPE is also the site of pathologic processes in a wide variety of retinal disorders including monogenic retinal dystrophies, age-related macular degeneration, and retinal detachment. Despite intense interest in the RPE, little is known about its molecular response to ocular damage or disease. We have conducted a comprehensive analysis of changes in transcript abundance (the “genomic response”) in the murine RPE after light damage. Several dozen transcripts, many related to cell–cell signaling, show significant increases in abundance in response to bright light; transcripts encoding visual cycle proteins show a decrease in abundance. Similar changes are induced by retinal detachment. Environmental and genetic perturbations that modulate the RPE response to bright light suggest that this response is controlled by the retina. In contrast to the response to bright light, the RPE response to retinal detachment overrides these modulatory affects.
The Lyric Suite and Berg's Twelve-Tone Duality
Authors: Ashby Arved
Published: September 2008

The Lyric Suite is Berg's first extended twelve-tone composition, yet by his own description only half of the work uses twelve-tone techniques. This compositional hybridity raises significant aesthetic and political questions. How could the composer demonstrate what he called “the possibility of expressing myself musically in that way” and at the same time artfully prevaricate on the issue of twelve-tone necessity? When in its genesis did the composer understand the Lyric Suite to be a hybrid composition? Here the sketches and autographs—held by the Österreichische Nationalbibliothek, Vienna—prove invaluable. Berg's sketches reveal that he began the Lyric Suite by working around the twelve-tone movements, which started with minimal experimental work that he did not keep. Berg attempted some kind of “twelve-tone music” with the Lyric Suite, but in failing to differentiate the compositional process from the supposedly pre-compositional, his approach was inconsistent with Schoenberg's early method of “working with tones.” At the same time, Schoenberg's and Webern's twelve-tone compositions from the early 1920s display hybrid aspects of their own. Berg came last of the three to twelve-tone methods and devised a typically artful response, going public with his amalgam and exhibiting it in the very fabric and design of his composition.
Berg's Propaganda Pieces: The “Platonic Idea” of Lulu
Authors: Notley Margaret
Published: September 2008

After finishing the short score of Lulu and starting to orchestrate it in the spring of 1934, Berg began to realize that his opera might not be staged in Berlin, long planned as the site for the premiere. In late May he decided to make a concert arrangement that he referred to as “a Propaganda selection,” which became the Symphonische Stücke aus “Lulu.” In contemporary usage the German word “Propaganda” typically denoted advertising or publicity. Acting on advice from his editor, Hans Heinsheimer, and supported by the efforts of his student Willi Reich, Berg sought to create a “Propaganda” work that could be performed even in Hitler's Germany and would drum up interest in performances of the entire opera elsewhere.

Letters and other sources, many unpublished, show Berg gradually coming to grips both with the reality of the political situation in Germany and with the offensiveness—even to some favorably disposed to modernist music—of the texts by Frank Wedekind on which he based his libretto. A comparison of his arrangement and the opera illuminates the different effects made by more or less the same music in the two works as well as what Berg valued in Lulu and was therefore reluctant to relinquish. Above all he resisted giving up the texts for the music that he arranged as the first and fifth movements, apparently wishing to preserve the striking textures that he had created by placing an operatic voice against a self-sufficient orchestral fabric. But mentored by Heinsheimer, he ended up distancing his arrangement from the opera that it was supposed to promote by removing most of the words; and assisted by Reich he wrote misleading program notes to fill in the resulting semantic gaps. Berg created an arrangement that could be enjoyed as, in his own words, “pure music.” Lulu became the platonic idea of Lulu.