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Methodological and statistical issues of quality of life (QoL) and economic evaluation in cancer clinical trials: report of a workshop.

In recent years, quality of life (QoL) and economic evaluations have become increasingly important as additional outcome measures in cancer clinical trials. However, both fields of research are relatively new and in need of finding solutions to a substantial number of specific methodological problems. This paper reports on the proceedings of a symposium aimed at summarising and discussing some of the most contentious methodological and statistical issues in QoL and economic evaluations. In addition, possible solutions are indicated and the most pertinent areas of research are identified. Issues specific to QoL evaluations that are addressed include clinically meaningful changes in QoL scores; how to analyse QoL data and to handle missing and censored data and integration of length of life and QoL outcomes. Issues specific to economic evaluations are the advantages and disadvantages of various outcome measures; statistical methods to analyse economic data and choice of decision criteria and analytical perspective. How to perform QoL and economic evaluations in large and simple trials and whether the gap between QoL and utility measures can be bridged are also discussed.

Clinical Trials as Topic↗

Multisite formative assessment for the Pathways study to prevent obesity in American Indian schoolchildren.

We describe the formative assessment process, using an approach based on social learning theory, for the development of a school-based obesity-prevention intervention into which cultural perspectives are integrated. The feasibility phase of the Pathways study was conducted in multiple settings in 6 American Indian nations. The Pathways formative assessment collected both qualitative and quantitative data. The qualitative data identified key social and environmental issues and enabled local people to express their own needs and views. The quantitative, structured data permitted comparison across sites. Both types of data were integrated by using a conceptual and procedural model. The formative assessment results were used to identify and rank the behavioral risk factors that were to become the focus of the Pathways intervention and to provide guidance on developing common intervention strategies that would be culturally appropriate and acceptable to all sites.

Asian People↗

Phytohormones in fungi: inter-kingdom modulators or fungal self-controlling elements?

SUMMARYLeveraging data from innovative experimental approaches, omics technologies, and bioinformatics, we offer new insights into how fungi communicate with and perceive their environment to achieve ecological success. By integrating comparative data from both the fungal and plant kingdoms, we critically reassessed the evolutionary, biochemical, and functional landscape of phytohormones in fungi, challenging the conventional notion that these molecules serve exclusively as plant regulators or as means of communication with them. Our analysis demonstrates that fungi not only synthesize a diverse array of phytohormones-including auxins, cytokinins, gibberellins, abscisic acid, ethylene, brassinosteroids, salicylic acid, and oxylipins-but also possess hormone-sensing and signal transduction mechanisms architecturally distinct from those of plants. Employing genomics, phylogenetics, and structural analyses, the review uncovers that many hormone biosynthetic and sensing pathways in fungi are evolutionarily ancient, sometimes predating their roles in plant-fungus interactions, and that some pathways show convergence rather than direct gene homology. Fungal phytohormones regulate development, growth, and metabolism, thereby playing key functions in their ecological context. The review emphasizes that, while biosynthetic pathways tend to be highly conserved, perception and signaling mechanisms in fungi are more varied and often remain poorly understood. We conclude that fungi have an intrinsic and autonomous hormonal physiology that underpins their ecological adaptability and success. Collectively, this analysis reframes fungal biology, highlighting the need for deeper investigation into the signaling and regulatory roles of phytohormones in fungi beyond their interactions with plants.

cell signaling↗

Molecular characterization of melanocyte stem cells in their niche.

Emerging evidence from stem cell (SC) research has strengthened the idea that SC fate is determined by a specialized environment, known as the SC niche. However, because of the difficulty of identifying individual stem cells and their surrounding components in situ, the exact mechanisms underlying SC regulation by the niche remain elusive. To overcome this difficulty, we employed melanocyte stem cells (MSCs), which allow the identification of individual SCs in the niche, the lower permanent portion of the hair follicle (HF). Here, we present molecular makers that can distinguish MSCs from other melanocyte (MC) subsets in the HF. We also describe a simple and robust method that allows gene expression profiling in individual SCs. After isolating individual MSCs from transgenic mice in which the MCs are marked by green fluorescence protein (GFP), we performed single-cell transcript analysis to obtain the molecular signature of individual MSCs in the niche. The data suggest the existence of a mechanism that induces the downregulation of various key molecules for MC proliferation or differentiation in MSCs located in the niche. By integrating these data, we propose that the niche is an environment that insulates SCs from various activating stimuli and maintains them in a quiescent state.

Animals↗

Architecture of a mediator for a bioinformatics database federation.

Developments in our ability to integrate and analyze data held in existing heterogeneous data resources can lead to an increase in our understanding of biological function at all levels. However, supporting ad hoc queries across multiple data resources and correlating data retrieved from these is still difficult. To address this, we are building a mediator based on the functional data model database, P/FDM, which integrates access to heterogeneous distributed biological databases. Our architecture makes use of the existing search capabilities and indexes of the underlying databases, without infringing on their autonomy. Central to our design philosophy is the use of schemas. We have adopted a federated architecture with a five-level schema, arising from the use of the ANSI-SPARC three-level schema to describe both the existing autonomous data resources and the mediator itself. We describe the use of mapping functions and list comprehensions in query splitting, producing execution plans, code generation, and result fusion. We give an example of cross-database querying involving data held locally in P/FDM systems and external data in SRS.

Algorithms↗

Virtual electronic patient records for shared care.

Systems that primarily serve health-care organizations are changing into systems that support patient care. The core of this change is shaped by systems for computer-based patient records (CPRs), which are part of local or regional networks, giving access to data in different information systems. In principle, it should not matter where the patient data are located as long as data can be transferred to the physical location where patients and clinicians meet. Networking and electronic communication enable to realize an environment that makes all systems where patient data reside, acting as one integrated, virtual CPR-system from the user's perspective. The patient record itself needs not to be physically located at one place, but may be virtual. A development in this direction is the European 14C project, which aims at integrating patient record data, images, and biosignals from whatever system they are stored and on whatever computer they are processed in the network.

Computer Communication Networks↗

Neutron spectrum measurements in the aluminum oxide filtered beam facility at the Brookhaven Medical Research Reactor.

Neutron spectrum measurements were performed on the aluminum oxide filter installed in the Brookhaven Medical Research Reactor (BMRR). For these measurements, activation foils were irradiated at the exit port of the beam facility. A technique based on dominant resonances in selected activation reactions was used to measure the epithermal neutron spectrum. The fast and intermediate-energy ranges of the neutron spectrum were measured by threshold reactions and 10B-shielded 235U fission reactions. Neutron spectral data were derived from the activation data by two approaches: (1) a short analysis which yields neutron flux values at the energies of the dominant or primary resonances in the epithermal activation reactions and integral flux data for neutrons above corresponding threshold or pseudo-threshold energies, and (2) the longer analysis which utilized all the activation data in a full-spectrum, unfolding process using the FERRET spectrum adjustment code. This paper gives a brief description of the measurement techniques, analysis methods, and the results obtained.

Aluminum Oxide↗

Neuroendocrine reactivity to nicotine in smokers.

The present study explored neuropeptide responses to nicotine from smoking. Habitual smokers smoked research cigarettes of known strength under controlled laboratory conditions while blood samples were withdrawn unobtrusively for subsequent biochemical analysis. To provide a metric that reflected total nicotine intake and total neurohormonal output, data were integrated over time. Subjects were relatively unresponsive in the low-nicotine (0.48 mg) condition. In the high-nicotine (2.87 mg) condition, there were significant positive correlations between integrated plasma nicotine and plasma arginine vasopressin (r = +0.985), its carrier protein neurophysin I (r = +0.944), and beta-endorphin-beta-lipotropin (r = +0.977), but not adrenocorticotropic hormone. Data from an experiment that used an extraction step to remove beta-lipotropin corroborated the functional relationship between plasma nicotine and beta-endorphin implied by the original findings. Taking into account recent research on the role of neuropeptides in the modulation of affective states and cognitive function as well as of other CNS activity, the present findings were interpreted as strengthening the hypothesis that nicotine-stimulated neuropeptide release provides positive reinforcement for smoking.

Adrenocorticotropic Hormone↗

Extended analysis of path data from mutant mice using the public domain software Wintrack.

Animal tracking by means of videocameras has made considerable progress over the past several years and is now being used in a large number of studies. However, the precision and frequency at which xy path data can be recorded using personal computers contrast with the relative simplicity of the analyses commonly conducted with this type of data. In order to achieve more analytical power and flexibility in numerical and graphical path analysis, we have developed Wintrack, a Windows application that processes data from a variety of commercially available tracking systems. The application provides an intuitive drag-and-drop interface to increase ease and speed of standard analysis and graphical representation of data. A flexible scripting language allows the advanced user to extend the capabilities of the program by defining custom arenas and specialized parameters. For example, this permits to integrate path data with events recorded through the keyboard or to adapt the program for the processing of GPS data from outdoors experiments. A macro language allows for fully automated and database-controlled large-scale data analysis. We are using this feature to develop new analysis parameters for water maze and open-field experiments and to evaluate them retrospectively with reference data from several thousand mice tested in our laboratory. For noncommercial use, the software can be downloaded free of charge at www.dpwolfer.ch/wintrack.

Animals↗

Pattern integrations in young depressed women: Part II.

Using Hildegard Peplau's theoretical model and focusing on the concept of pattern integrations, clinical data from a pilot intervention program for depressed women were analyzed. The program consisted of a collaborative relationship between primary-care providers and two Psychiatric-Mental Health Clinical Nurse Specialists in which women experiencing symptoms of depression were identified and referred to the research program. Data derived from clinical intervention done over a 4-month period with 6 women (42 hours of clinical tapes) was used for analysis. Clusters of behaviors constituting pattern integrations were analyzed for the reciprocal interactions of the nurses and the clients. Four pattern integrations common to the women in the sample were identified. Clinical examples and a framework for intervention using the patterns integrations is presented.

Adolescent↗

Understanding cultural significance, the edible mushrooms case.

BACKGROUND: Cultural significance is a keystone in quantitative ethnobiology, which offers the possibility to make inferences about traditional nomenclature systems, use, appropriation and valuing of natural resources. In the present work, using as model the traditional mycological knowledge of Zapotecs from Oaxaca, Mexico, we analyze the cultural significance of wild edible resources. METHODS: In 2003 we applied 95 questionnaires to a random sample of informants. With this data we integrated the Edible Mushroom Cultural Significance Index. This index included eight variables: frequency of mention, perceived abundance, use frequency, taste, multifunctional food use, knowledge transmission, health and economy. Data were analyzed in an inductive perspective using ordination and grouping techniques to reveal the behavior of species in a cultural multivariate dimension. RESULTS: In each variable the species had different conducts. Cantharellus cibarius s.l. was the species with most frequency of mention. Pleurotus sp. had the highest perceived abundance. C. cibarius s.l. was the most frequently consumed species. Gomphus clavatus was the most palatable species and also ranked highest in the multifunctional food index. Cortinarius secc. Malacii sp. had the highest traditional importance. Only Tricholoma magnivelare was identified as a health enhancer. It also had the most economic importance. According to the compound index, C. cibarius s.l., the Amanita caesarea complex, Ramaria spp. and Neolentinus lepideus were the mushrooms with highest cultural significance. Multivariate analysis showed that interviewees identify three main groups of mushrooms: species with high traditional values, frequent consumption and known by the majority; species that are less known, infrequently consumed and without salient characteristics; and species with low traditional values, with high economic value and health enhancers. CONCLUSION: The compound index divided the cultural significance into several cultural domains and showed the causes that underlie this phenomenon. This approach can be used in cross-cultural studies because it brings a list with the relative position of species among a cultural significance gradient. This list is suitable for comparisons and also it is flexible because cultural variables can be included or removed to adjust it to the nature of the different cultures or resources under study.

Adult↗

The Observer Video-Pro: new software for the collection, management, and presentation of time-structured data from videotapes and digital media files.

The Observer Video-Pro is a system for collecting, managing, analyzing, and presenting observational data. It integrates The Observer software with time code and multimedia hardware components. It extends the functionality of a conventional real-time event recording program in various ways. Observational data can be collected, reviewed, and edited with synchronized display of the corresponding video images. For optimal visual feedback during coding, one can display the video image in a window on the computer screen. Video playback from either a VCR or a digital media file can be controlled by the computer, allowing software-controlled jog, shuttle, and search functions. Besides a wide range of VCRs, The Observer Video-Pro supports all major digital video file formats. The software allows the user to summarize research findings in numerical, graphical, or multimedia format. One can create a time--event plot for a quick glance at the temporal structure of the observed process, or run specific analysis procedures and generate reports with statistics. An Event Summary function is available for exploratory and qualitative analysis. Video material can be summarized in a Video Play List, which allows on-screen summary presentations or the creation of highlight compilations on tape, CD, or other media. Video images can be captured and saved as disk files, for use as illustrations in documents, slides for presentations, and so forth. In this paper we describe the design and operation of the system, illustrated with a case study from research on Repetitive Strain Injury (RSI).

Electronic Data Processing↗

Web architecture for the remote browsing and analysis of distributed medical images and data.

To provide easy retrieval, integration and evaluation of multimodal medical images and data in a web browser environment, distributed application technologies and Java programming were used to develop a client-server architecture based on software agents. The server side manages secure connections and queries to heterogeneous remote databases and file systems containing patient personal and clinical data. The client side is a Java applet running in a web browser and providing a friendly medical user interface to perform queries on patient and medical test data and integrate and visualize properly the various query results. A set of tools based on Java Advanced Imaging API enables to process and analyze the retrieved bioimages, and quantify their features in different regions of interest. The platform-independence Java technology makes the developed prototype easy to be managed in a centralized form and provided in each site where an intranet or internet connection can be located. Giving the healthcare providers effective tools for browsing, querying, visualizing and evaluating comprehensively medical images and records in all locations where they can need them - e.g. emergency, operating theaters, ward, or even outpatient clinics- the implemented prototype represents an important aid in providing more efficient diagnoses and medical treatments.

Ambulatory Care Facilities↗

A population-based study of skin cancer incidence and prevalence in renal transplant recipients.

BACKGROUND: Cancers occurring following solid organ transplantation are a rapidly growing public health concern. Defining the extent of the problem has been limited by surveillance systems with incomplete registration of cases and the paucity of reliable national incidence data. OBJECTIVES: To determine the incidence of all cancers following renal transplantation and to make a detailed examination of trends and patterns associated with postrenal transplant skin cancers. METHODS: Integration of data from the national renal transplant database and the national cancer registry in Ireland enabled accurate determination of the number of renal transplant recipients (RTRs) with skin cancers and other malignancies in the time period 1 January 1994 to 31 December 2001. RESULTS: We demonstrated a biphasic increase in skin cancer incidence following renal transplantation, determined by the age at transplantation. There was a steady increase in risk for older RTRs (age 50+ years) from year 2 post-transplant, whereas the increased risk in younger RTRs (age < 50 years) occurred later but much more significantly, reaching 200 times the risk for an age-matched nontransplanted population by year 6 post-transplant. The number of nonmelanoma skin cancers (NMSCs) registered in RTRs accounted for 1% of all NMSCs registered nationally over the study period. The standardized incidence rates for invasive NMSC (33-fold increase) and in situ carcinoma of the skin (65-fold increase) were significantly increased (P < 0.05). The risk for invasive squamous cell carcinoma (SCC) was increased 82-fold compared with the nontransplanted population. Male RTRs were at particular risk of invasive SCC at sun-exposed sites such as the scalp and the external ear. Risk of malignant melanoma and Kaposi sarcoma were also increased relative to the nontransplanted population. CONCLUSIONS: This comprehensive national study illustrates how rates of skin cancer in Irish RTRs have influenced the national incidence of skin cancer. The high incidence of SCC, basal cell carcinoma and Bowen's disease in the early post-transplant period for older patients and the cumulative risk in younger patients with increased duration of transplantation highlight the importance of implementing early and continued cancer surveillance regimens post-transplant.

Adult↗

A structural model of 20S immunoproteasomes: effect of LMP2 codon 60 polymorphism on expression, activity, intracellular localisation and insight into the regulatory mechanisms.

The immunoproteasome subunit low molecular weight protein 2 (LMP2) codon 60 polymorphism has been associated with autoimmune diseases. It has also been demonstrated to influence susceptibility to TNF-alpha-induced apoptosis in blood cells and proteasome activity in aged human brain. In the present study, an in silico model of immunoproteasome was used to examine the effect of the R60H polymorphism in the LMP2 subunit. The investigation of immunoproteasome expression, activity and intracellular localisation in an in vitro cellular model, namely lymphoblastoid cell lines, showed no major variations in functionality and amount, while a significant difference in antibody affinity was apparent. These data were integrated with previous results obtained in different tissues and combined with a structural model of the LMP2 polymorphism. Accordingly, we identified three prospective mechanisms that could explain the biological data for the polymorphism, such as modulation of the binding affinity of a putative non-catalytic modifier site on the external surface of the immunoproteasome core, or the modification of any channel between alpha and beta rings.

Antibodies, Monoclonal↗

Peer, family integration and other determinants of cannabis use among teenagers.

Cannabis consumption is on the rise in the French-speaking Community of Belgium, especially among teenagers. The physical and mental harms related to that drug prompted us to search for factors associated with cannabis consumption. The aim of this paper is thus to identify a series of potential predictors of teenager's cannabis use and particularly the influence of peer and family integration. The data analyzed were taken from the 1998 data bank "Health Behavior in School-Aged Children", an international quantitative cross-national study, which takes place every four years. The variables investigated were peer and family integration and the habit of drug consumption (tobacco, alcohol or a narcotic other than cannabis) as potential determinants of the experimentation, current usage of cannabis (at least once a month) and regular usage (at least once a week). Apart from the socio-demographic variables, these predictors were investigated by univariate and multivariate analysis (logistic regression). The analyses covered 744 students in Catholic high schools. Results showed that 30.2% of students had tried to smoke cannabis and 50% of them continued to smoke it at least during the previous month. Age, number of income in the family, strong peer group integration [OR 7.7; CI 95% (3.5;17.3)] and drug-consumption habit [for example, tobacco use: OR 7.4; CI 95% (4.8;11.32)] were associated with cannabis experimentation. Age, gender, nationality, average family integration [OR 2.13; CI 95% (1.1;4.1)] and other drugs use as addiction to nicotine [OR 9.5; CI 95% (5.6;16.3)] determined the current consumption of the substance. Preventive action should aim at improving the teenager's integration into the family circle in order to prevent the trial and consumption of cannabis. In addition, prevention should include the consumption of (addictive) substances in general.

Adolescent↗

Statistical issues and challenges associated with rapid detection of bio-terrorist attacks.

The traditional focus for detecting outbreaks of an epidemic or bio-terrorist attack has been on the collection and analysis of medical and public health data. Although such data are the most direct indicators of symptoms, they tend to be collected, delivered, and analysed days, weeks, and even months after the outbreak. By the time this information reaches decision makers it is often too late to treat the infected population or to react in some other way. In this paper, we explore different sources of data, traditional and non-traditional, that can be used for detecting a bio-terrorist attack in a timely manner. We set our discussion in the context of state-of-the-art syndromic surveillance systems and we focus on statistical issues and challenges associated with non-traditional data sources and the timely integration of multiple data sources for detection purposes.

Bioterrorism↗