Paper 3: EUROCAT data quality indicators for population-based registries of congenital anomalies.

The European Surveillance of Congenital Anomalies (EUROCAT) network of population-based congenital anomaly registries is an important source of epidemiologic information on congenital anomalies in Europe covering live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly. EUROCAT's policy is to strive for high-quality data, while ensuring consistency and transparency across all member registries. A set of 30 data quality indicators (DQIs) was developed to assess five key elements of data quality: completeness of case ascertainment, accuracy of diagnosis, completeness of information on EUROCAT variables, timeliness of data transmission, and availability of population denominator information. This article describes each of the individual DQIs and presents the output for each registry as well as the EUROCAT (unweighted) average, for 29 full member registries for 2004-2008. This information is also available on the EUROCAT website for previous years. The EUROCAT DQIs allow registries to evaluate their performance in relation to other registries and allows appropriate interpretations to be made of the data collected. The DQIs provide direction for improving data collection and ascertainment, and they allow annual assessment for monitoring continuous improvement. The DQI are constantly reviewed and refined to best document registry procedures and processes regarding data collection, to ensure appropriateness of DQI, and to ensure transparency so that the data collected can make a substantial and useful contribution to epidemiologic research on congenital anomalies.

Planning and conducting focus group research with nurses.

Focus groups are increasingly popular in nursing research. However, proper care and attention are critical to their planning and conduct, particularly those involving nursing staff. This article uses data gleaned from prior research to address the complexities present in clinical settings when conducting focus groups with nurses. Applying their combined experiences of conducting studies with nursing staff, the authors present a data-derived approach to thorough preparation and successful implementation of focus group research, offering a unique contribution to the literature regarding this research strategy.

NanoImpactNet - Stakeholders' knowledge needs for research on the health and environmental impact of nanomaterials

NanoImpactNet (NIN) is a multidisciplinary European Commission funded network on the environmental, health and safety (EHS) impact of nanomaterials. The 24 founding scientific institutes are leading European research groups active in the fields of nanosafety, nanorisk assessment and nanotoxicology. This 4−year project is the new focal point for information exchange within the research community. Contact with other stakeholders is vital and their needs are being surveyed. NIN is communicating with 100s of stakeholders: businesses; internet platforms; industry associations; regulators; policy makers; national ministries; international agencies; standard−setting bodies and NGOs concerned by labour rights, EHS or animal welfare. To improve this communication, internet research, a questionnaire distributed via partners and targeted phone calls were used to identify stakeholders' interests and needs. Knowledge gaps and the necessity for further data mentioned by representatives of all stakeholder groups in the targeted phone calls concerned: potential toxic and safety hazards of nanomaterials throughout their lifecycles; fate and persistence of nanoparticles in humans, animals and the environment; risks associated to nanoparticle exposure; participation in the preparation of nomenclature, standards, methodologies, protocols and benchmarks; development of best practice guidelines; voluntary schemes on responsibility; databases of materials, research topics and themes. Findings show that stakeholders and NIN researchers share very similar knowledge needs, and that open communication and free movement of knowledge will benefit both researchers and industry. Consequently NIN will encourage stakeholders to be active members. These survey findings will be used to improve NIN's communication tools to further build on interdisciplinary relationships towards a healthy future with nanotechnology.

Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data.

Despite the central role of quantitative PCR (qPCR) in the quantification of mRNA transcripts, most analyses of qPCR data are still delegated to the software that comes with the qPCR apparatus. This is especially true for the handling of the fluorescence baseline. This article shows that baseline estimation errors are directly reflected in the observed PCR efficiency values and are thus propagated exponentially in the estimated starting concentrations as well as 'fold-difference' results. Because of the unknown origin and kinetics of the baseline fluorescence, the fluorescence values monitored in the initial cycles of the PCR reaction cannot be used to estimate a useful baseline value. An algorithm that estimates the baseline by reconstructing the log-linear phase downward from the early plateau phase of the PCR reaction was developed and shown to lead to very reproducible PCR efficiency values. PCR efficiency values were determined per sample by fitting a regression line to a subset of data points in the log-linear phase. The variability, as well as the bias, in qPCR results was significantly reduced when the mean of these PCR efficiencies per amplicon was used in the calculation of an estimate of the starting concentration per sample.

Gene expression databases and data mining.

The DNA microarray technology has arguably caught the attention of the worldwide life science community and is now systematically supporting major discoveries in many fields of study. The majority of the initial technical challenges of conducting experiments are being resolved, only to be replaced with new informatics hurdles, including statistical analysis, data visualization, interpretation, and storage. Two systems of databases, one containing expression data and one containing annotation data are quickly becoming essential knowledge repositories of the research community. This present paper surveys several databases, which are considered "pillars" of research and important nodes in the network. This paper focuses on a generalized workflow scheme typical for microarray experiments using two examples related to cancer research. The workflow is used to reference appropriate databases and tools for each step in the process of array experimentation. Additionally, benefits and drawbacks of current array databases are addressed, and suggestions are made for their improvement.

Family Well-Being and Family Policy - A Review of Research on Benefits and Costs

This report is published under the Springboard Initiative. It is designed to assist in the process of mapping out the complex issues and data requirements which arise in developing policies for families and in finding actions which are known to promote family well-being Download the Report here

Selecting control genes for RT-QPCR using public microarray data.

Background: Gene expression analysis has emerged as a major biological research area, with real-time quantitative reverse transcription PCR (RT-QPCR) being one of the most accurate and widely used techniques for expression profiling of selected genes. In order to obtain results that are comparable across assays, a stable normalization strategy is required. In general, the normalization of PCR measurements between different samples uses one to several control genes (e. g. housekeeping genes), from which a baseline reference level is constructed. Thus, the choice of the control genes is of utmost importance, yet there is not a generally accepted standard technique for screening a large number of candidates and identifying the best ones. Results: We propose a novel approach for scoring and ranking candidate genes for their suitability as control genes. Our approach relies on publicly available microarray data and allows the combination of multiple data sets originating from different platforms and/or representing different pathologies. The use of microarray data allows the screening of tens of thousands of genes, producing very comprehensive lists of candidates. We also provide two lists of candidate control genes: one which is breast cancer-specific and one with more general applicability. Two genes from the breast cancer list which had not been previously used as control genes are identified and validated by RT-QPCR. Open source R functions are available at http://www.isrec.isb-sib.ch/similar to vpopovic/research/ Conclusion: We proposed a new method for identifying candidate control genes for RT-QPCR which was able to rank thousands of genes according to some predefined suitability criteria and we applied it to the case of breast cancer. We also empirically showed that translating the results from microarray to PCR platform was achievable.

Current genetic data do not improve the prediction of type 2 diabetes mellitus: the CoLaus study.

CONTEXT: Several genetic risk scores to identify asymptomatic subjects at high risk of developing type 2 diabetes mellitus (T2DM) have been proposed, but it is unclear whether they add extra information to risk scores based on clinical and biological data. OBJECTIVE: The objective of the study was to assess the extra clinical value of genetic risk scores in predicting the occurrence of T2DM. DESIGN: This was a prospective study, with a mean follow-up time of 5 yr. SETTING AND SUBJECTS: The study included 2824 nondiabetic participants (1548 women, 52 ± 10 yr). MAIN OUTCOME MEASURE: Six genetic risk scores for T2DM were tested. Four were derived from the literature and two were created combining all (n = 24) or shared (n = 9) single-nucleotide polymorphisms of the previous scores. A previously validated clinic + biological risk score for T2DM was used as reference. RESULTS: Two hundred seven participants (7.3%) developed T2DM during follow-up. On bivariate analysis, no differences were found for all but one genetic score between nondiabetic and diabetic participants. After adjusting for the validated clinic + biological risk score, none of the genetic scores improved discrimination, as assessed by changes in the area under the receiver-operating characteristic curve (range -0.4 to -0.1%), sensitivity (-2.9 to -1.0%), specificity (0.0-0.1%), and positive (-6.6 to +0.7%) and negative (-0.2 to 0.0%) predictive values. Similarly, no improvement in T2DM risk prediction was found: net reclassification index ranging from -5.3 to -1.6% and nonsignificant (P ≥ 0.49) integrated discrimination improvement. CONCLUSIONS: In this study, adding genetic information to a previously validated clinic + biological score does not seem to improve the prediction of T2DM.

2006 National report (2005 data) to the EMCDDA by the Reitox National Focal Point: Norway: New developments, trends and in-depth information on selected issues.

This is a 2006 national report to the EMCDDA, using 2005 data. It is compiled by the Reitox national focal point and covers epidemiology, policing, strategy, drugs markets, drug-related infectious diseases, drug-related death and problem drug use in Norway.This resource was contributed by The National Documentation Centre on Drug Use.

The UniProtKB/Swiss-Prot Tox-Prot program: A central hub of integrated venom protein data.

Animal toxins are of interest to a wide range of scientists, due to their numerous applications in pharmacology, neurology, hematology, medicine, and drug research. This, and to a lesser extent the development of new performing tools in transcriptomics and proteomics, has led to an increase in toxin discovery. In this context, providing publicly available data on animal toxins has become essential. The UniProtKB/Swiss-Prot Tox-Prot program (http://www.uniprot.org/program/Toxins) plays a crucial role by providing such an access to venom protein sequences and functions from all venomous species. This program has up to now curated more than 5000 venom proteins to the high-quality standards of UniProtKB/Swiss-Prot (release 2012_02). Proteins targeted by these toxins are also available in the knowledgebase. This paper describes in details the type of information provided by UniProtKB/Swiss-Prot for toxins, as well as the structured format of the knowledgebase.

The Irish alcohol misuser in England: Ill served by research and policy? Some suggestions for future research opportunities.

Inequalities in the physical and psychological health of the first- and second-generation Irish subjects have been well documented. Despite the fact that the Irish alcohol misuser is subject to a number of unhelpful stereotypes, the research concerning alcohol misuse in the Irish is surprisingly sparse. What little exists indicates that Irish alcohol misusers tend to fit the profile of the "chronic alcoholic." Specifically, they tend to be older (45 years +) and to have impaired physical and psychological health. Not surprisingly this is accompanied by poor longitudinal outcomes. Furthermore, alcohol problems worsen as a result of migration (this phenomenon is not restricted to the UK). Alcohol and drug services are now frequently merged, and policy is directed towards the visible young illicit drug user. This paper argues that inadvertently Irish alcohol misusers are discriminated against as a result. Future avenues of research are outlined to provide services and policy makers with data to plan services taking full account of the needs of Irish alcohol misusers.This resource was contributed by The National Documentation Centre on Drug Use.

Alcohol-related and hepatocellular cancer deaths by country of birth in England and Wales: analysis of mortality and census data.

BACKGROUND: The incidence of and mortality from alcohol-related conditions, liver disease and hepatocellular cancer (HCC) are increasing in the UK. We compared mortality rates by country of birth to explore potential inequalities and inform clinical and preventive care. DESIGN: Analysis of mortality for people aged 20 years and over using the 2001 Census data and death data from 1999 and 2001-2003. SETTING: England and Wales. MAIN OUTCOME MEASURES: Standardized mortality ratios (SMRs) for alcohol-related deaths and HCC. RESULTS: Mortality from alcohol-related deaths (23 502 deaths) was particularly high for people born in Ireland (SMR for men [M]: 236, 95% confidence interval [CI]: 219-254; SMR for women [F]: 212, 95% CI: 191-235) and Scotland (SMR-M: 187, CI: 173-213; SMR-F 182, CI: 163-205) and men born in India (SMR-M: 161, CI: 144-181). Low alcohol-related mortality was found in women born in other countries and men born in Bangladesh, Middle East, West Africa, Pakistan, China and Hong Kong, and the West Indies. Similar mortality patterns were observed by country of birth for alcoholic liver disease and other liver diseases. Mortality from HCC (8266 deaths) was particularly high for people born in Bangladesh (SMR-M: 523, CI: 380-701; SMR-F: 319, CI: 146-605), China and Hong Kong (SMR-M: 492, CI: 168-667; SMR-F: 323, CI: 184-524), West Africa (SMR-M: 440, CI, 308-609; SMR-F: 319, CI: 165-557) and Pakistan (SMR-M: 216, CI: 113-287; SMR-F: 215, CI: 133-319). CONCLUSIONS: These findings show persistent differences in mortality by country of birth for both alcohol-related and HCC deaths and have important clinical and public health implications. New policy, research and practical action are required to address these differences.This resource was contributed by The National Documentation Centre on Drug Use.

Interpretation of array comparative genome hybridization data: a major challenge.

The advent and application of high-resolution array-based comparative genome hybridization (array CGH) has led to the detection of large numbers of copy number variants (CNVs) in patients with developmental delay and/or multiple congenital anomalies as well as in healthy individuals. The notion that CNVs are also abundantly present in the normal population challenges the interpretation of the clinical significance of detected CNVs in patients. In this review we will illustrate a general clinical workflow based on our own experience that can be used in routine diagnostics for the interpretation of CNVs.