Bayesian networks for evaluating forensic DNA profiling evidence: a review and guide to literature

Almost 30 years ago, Bayesian networks (BNs) were developed in the field of artificial intelligence as a framework that should assist researchers and practitioners in applying the theory of probability to inference problems of more substantive size and, thus, to more realistic and practical problems. Since the late 1980s, Bayesian networks have also attracted researchers in forensic science and this tendency has considerably intensified throughout the last decade. This review article provides an overview of the scientific literature that describes research on Bayesian networks as a tool that can be used to study, develop and implement probabilistic procedures for evaluating the probative value of particular items of scientific evidence in forensic science. Primary attention is drawn here to evaluative issues that pertain to forensic DNA profiling evidence because this is one of the main categories of evidence whose assessment has been studied through Bayesian networks. The scope of topics is large and includes almost any aspect that relates to forensic DNA profiling. Typical examples are inference of source (or, 'criminal identification'), relatedness testing, database searching and special trace evidence evaluation (such as mixed DNA stains or stains with low quantities of DNA). The perspective of the review presented here is not exclusively restricted to DNA evidence, but also includes relevant references and discussion on both, the concept of Bayesian networks as well as its general usage in legal sciences as one among several different graphical approaches to evidence evaluation.

Development of place navigation in rats from weaning to puberty.

Young hooded rats were trained to escape onto a hidden platform after swimming in a pool of opaque water. Subjects 21, 28, 35, 42, and 64 days of age on the first training day were given 28 trials on 5 consecutive days. Half of the rats were required to localize the platform in relation to external room cues only ("place only" condition) and the other half were helped by the presence of a visible cue on the platform ("cue + place" condition). A deficiency in place navigation was observed in the 21- and 28-day groups; they showed slow escape and took circuitous routes more often than older rats. This deficiency was related to a poor spatial bias toward the training position when the subjects were allowed to swim for 30 s in the absence of the platform, at the end of the 28-trial training period (probe trial). The 35-day group showed adult-like learning ability in both training conditions, but failed to show searching behavior during the probe trial after having been trained in the presence of the proximal cue. Only rats older than 40 days showed typical adult behavior such as swimming directly toward the platform from any starting position and localized searching around the absent platform's position during the probe trial, no matter what the training conditions were. These results suggest that central nervous system structures responsible for place learning in the rat are functional from around 32 days of age, but fail to trigger searching behavior following cued training before the sixth week.

PRPF31 alternative splicing and expression in human retina

PURPOSE: To provide a mechanistic link between mutations in PRPF31, and essential and ubiquitously expressed gene, and retinitis pigmentosa, a disorder restricted to the eye. METHODS: We investigated the existence of retina-specific PRPF31 isoforms and the expression of this gene in human retina and other tissues, as well as in cultured human cell lines. PRPF31 transcripts were examined by RT-PCR, quantitative PCR, cloning and sequencing. RESULTS: Database searching revealed the presence of a retina-specific PRPF31 isoform in mouse. However, this isoform could not be experimentally identified in transcripts from human retina or from a human whole eye. Nevertheless, four different PRPF31 isoforms, that were common to all analyzed tissues and cell lines, were isolated. Three of these harbored the full-length PRPF31 coding sequence, whereas the fourth was very short and probably non-coding. The amount of PRPF31 mRNA was previously found to be lower in patients with mutations in this gene than in healthy individuals, making it likely that retinal cells are more sensitive to variation in PRPF31 expression. However, quantitative PCR experiments revealed that PRPF31 mRNA levels in human retina were comparable to those detected in other tissues. CONCLUSIONS: Our results show that the retina-restricted phenotype caused by PRPF31 mutations cannot be explained by the presence of tissue-specific isoforms, or by differential expression of PRPF31 in the retina. As a consequence, the etiology of PRPF31-associated retinitis pigmentosa likely relies on other, probably more subtle molecular mechanisms.

The economic burden of alcohol dependence in europe.

AIMS: To determine the economic burden pertaining to alcohol dependence in Europe. METHODS: Database searching was combined with grey literature searching to identify costs and resource use in Europe relating to alcohol dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) or the World Health Organisation's International Classification of Diseases (ICD-10). Searches combined MeSH headings for both economic terms and terms pertaining to alcohol dependence. Relevant outcomes included direct healthcare costs and indirect societal costs. Main resource use outcomes included hospitalization and drug costs. RESULTS: Compared with the number of studies of the burden of alcohol use disorders in general, relatively few focussed specifically on alcohol dependence. Twenty-two studies of variable quality were eligible for inclusion. The direct costs of alcohol dependence in Europe were substantial, the treatment costs for a single alcohol-dependent patient lying within the range euro1591-euro7702 per hospitalization and the annual total direct costs accounting for 0.04-0.31% of an individual country's gross domestic product (GDP). These costs were driven primarily by hospitalization; in contrast, the annual drug costs for alcohol dependence were low. The indirect costs were more substantial than the direct costs, accounting for up to 0.64% of GDP per country annually. Alcohol dependence may be more costly in terms of health costs per patient than alcohol abuse. CONCLUSIONS: This review confirms that alcohol dependence represents a significant burden for European healthcare systems and society. Difficulties in comparing across cost-of-illness studies in this disease area, however, prevent specific estimation of the economic burden.

Angiotensin converting enzyme inhibitor induced angio-oedema: a review of the pathophysiology and risk factors.

Angio-oedema (AE) is a known adverse effect of angiotensin converting enzyme inhibitor (ACE-I) therapy. Over the past several decades, evidence of failure to diagnose this important and potentially fatal reaction is commonly found in the literature. Because this reaction is often seen first in the primary care setting, a review was undertaken to analyse and document the keys to both diagnostic criteria as well as to investigate potential risk factors for ACE-I AE occurrence. A general review of published literature was conducted through Medline, EMBASE, and the Cochrane Database, targeting ACE-I-related AE pathomechanism, diagnosis, epidemiology, risk factors, and clinical decision making and treatment. The incidence and severity of AE appears to be on the rise and there is evidence of considerable delay in diagnosis contributing to significant morbidity and mortality for patients. The mechanism of AE due to ACE-I drugs is not fully understood, but some genomic and metabolomic information has been correlated. Additional epidemiologic data and clinical treatment outcome predictors have been evaluated, creating a basis for future work on the development of clinical prediction tools to aid in risk identification and diagnostic differentiation. Accurate recognition of AE by the primary care provider is essential to limit the rising morbidity associated with ACE-I treatment-related AE. Research findings on the phenotypic indicators relevant to this group of patients as well as basic research into the pathomechanism of AE are available, and should be used in the construction of better risk analysis and clinical diagnostic tools for ACE-I AE.

Partitioning of reproduction in animal societies.

A key feature differentiating cooperative animal societies Is the apportionment of reproduction among individuals. Only recently have studies started to focus on intraspecific variability in the distribution of reproduction within animal societies, and the available data suggest that this variability might be greater than previously suspected. How can one account for intra-and interspecific variability in partitioning of reproduction? This Is one of the most intriguing problems in the study of social behaviour, and understanding the factors underlying this variability is one of the keys to understanding the properties of complex animal societies.

Small and long non-coding RNAs in cardiac homeostasis and regeneration

Cardiovascular diseases and in particular heart failure are major causes of morbidity and mortality in the Western world. Recently, the notion of promoting cardiac regeneration as a means to replace lost cardiomyocytes in the damaged heart has engendered considerable research interest. These studies envisage the utilization of both endogenous and exogenous cellular populations, which undergo highly specialized cell fate transitions to promote cardiomyocyte replenishment. Such transitions are under the control of regenerative gene regulatory networks, which are enacted by the integrated execution of specific transcriptional programs. In this context, it is emerging that the non-coding portion of the genome is dynamically transcribed generating thousands of regulatory small and long non-coding RNAs, which are central orchestrators of these networks. In this review, we discuss more particularly the biological roles of two classes of regulatory non-coding RNAs, i.e. microRNAs and long non-coding RNAs, with a particular emphasis on their known and putative roles in cardiac homeostasis and regeneration. Indeed, manipulating non-coding RNA-mediated regulatory networks could provide keys to unlock the dormant potential of the mammalian heart to regenerate. This should ultimately improve the effectiveness of current regenerative strategies and discover new avenues for repair. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.

Why bystanders decline telephone cardiac resuscitation advice.

OBJECTIVES: The aim of this study was to evaluate the rate and reason for refusal of telephone-based cardiopulmonary resuscitation (CPR) instruction by bystanders after the implementation of the dispatch center's systematic telephone CPR protocol. METHODS: Over a 15-month period the authors prospectively collected all case records from the emergency medical services (EMS) dispatch center when CPR had been proposed to the bystander calling in and recorded the reason for declining or not performing that the bystander spontaneously mentioned. All pediatric and adult traumatic and nontraumatic cases were included. Situations when resuscitation had been spontaneously initiated by bystanders were excluded. RESULTS: During the study period, dispatchers proposed CPR on 264 occasions: 232 adult nontraumatic cases, 17 adult traumatic cases, and 15 pediatric (traumatic and nontraumatic) cases. The proposal was accepted in 163 cases (61.7%, 95% confidence interval [CI] = 54.6% to 66.5%), and CPR was eventually performed in 134 cases (51%, 95% CI = 43.2% to 55.3%). In 35 of the cases where resuscitation was not carried out, the condition of the patient or conditions at the scene made this decision medically appropriate. Of the remaining 95 cases, 55 were due to physical limitations of the caller, and 33 were due to emotional distress. CONCLUSIONS: The telephone CPR acceptance rate of 62% in this study is comparable to those of other similar studies. Because bystanders' physical condition is one of the keys to success, the rate may not improve as the population ages.

How T cell receptors interact with peptide-MHCs: A multiple steered molecular dynamics study.

The T-cell receptor (TCR) interaction with antigenic peptides (p) presented by the major histocompatibility complex (MHC) molecule is a key determinant of immune response. In addition, TCR-pMHC interactions offer examples of features more generally pertaining to protein-protein recognition: subtle specificity and cross-reactivity. Despite their importance, molecular details determining the TCR-pMHC binding remain unsolved. However, molecular simulation provides the opportunity to investigate some of these aspects. In this study, we perform extensive equilibrium and steered molecular dynamics simulations to study the unbinding of three TCR-pMHC complexes. As a function of the dissociation reaction coordinate, we are able to obtain converged H-bond counts and energy decompositions at different levels of detail, ranging from the full proteins, to separate residues and water molecules, down to single atoms at the interface. Many observed features do not support a previously proposed two-step model for TCR recognition. Our results also provide keys to interpret experimental point-mutation results. We highlight the role of water both in terms of interface resolvation and of water molecules trapped in the bound complex. Importantly, we illustrate how two TCRs with similar reactivity and structures can have essentially different binding strategies. Proteins 2011; © 2011 Wiley-Liss, Inc.

Group 4: Career development for diverse and underserved populations

Globalization and diverse populations due to migration imply that counselors are expected to deliver career services to populations from a large array of cultural settings. Moreover, individuals belonging to minority or non-dominant groups may be underserved or misserved, thus decreasing their chances of finding employment opportunities through career counseling. To develop specific interventions minority or non-dominant groups, it seems important to understand their strength and weaknesses. These strengths and weaknesses will be presented in terms of risk and resilience factors, such as low future orientation and social support respectively. In the last two decades, several authors have made contributions to adapt and improve career services in order to best meet these minority groups' needs. A review of this literature identified thirteen keys to effective practice. For example, one key is to take responsibility for one's own biases and prejudices. Nonetheless, some underserved groups remain difficult to identify. Comparing some basic national demographic data with data from our counseling centers may be helpful in this context in identifying specific groups and assessing needs. One solution, in order to promote social justice across (all) cultural groups, is to encourage multiculturalism in both career counseling and society as a whole. A more inclusive society would allow each person in a minority or non-dominant group to contribute more effectively to the development and growth of this society.

Care related pain in rehabilitation after orthopedic trauma: An exploratory study with qualitative data.

OBJECTIVE: Care related pain (CRP) is generally under-estimated and rarely studied in rehabilitation as well as in general medecine. Beliefs about pain influence psychological distress, adjustment to pain and physical disability. In this sense, perceptions of CRP could limit recovery. This exploratory study aims to understand patients' and caregivers' subjective perceptions and beliefs about CRP. PATIENTS AND METHODS: Questionnaires about CRP were submitted to members of the interdisciplinary team of a rehabilitation hospital and to patients with musculoskeletal complaints (cross-sectional design). Twenty patients were also individually interviewed (qualitative data). Four topics were addressed: frequency of CRP, situations and procedures causing CRP, beliefs about CRP and means used to deal with CRP. RESULTS: Seventy-five caregivers and 50 patients replied to the questionnaire. CRP is a very common experience in rehabilitation and it is recognized by both groups. Generally, the situations causing CRP reflect the specificity of rehabilitation (mobilization...) and are similarly perceived by patients and caregivers, with patients considering them as more painful. Beliefs about CRP are clearly different from those usually associated with pain. Both groups point out the utilitarian and the inevitable character of CRP. They differ on that, that patients had a more positive view about CRP. They associate it more often with progress and see it as acceptable at least until a certain limit. They are also able to perceive the richness of means used by physiotherapists to help them coping with CRP. CONCLUSION: Our data may suggest new keys to motivate patient to be active in rehabilitation for example in choosing carefully arguments or words which may fit theirs' beliefs about CRP, or in using various means to manage CRP. Promoting the use of relational competences with chronic pain patients and of a patient-centred approach may also be a concern in training caregivers.

Correlative microscopy.

In recent years correlative microscopy, combining the power and advantages of different imaging system, e.g., light, electrons, X-ray, NMR, etc., has become an important tool for biomedical research. Among all the possible combinations of techniques, light and electron microscopy, have made an especially big step forward and are being implemented in more and more research labs. Electron microscopy profits from the high spatial resolution, the direct recognition of the cellular ultrastructure and identification of the organelles. It, however, has two severe limitations: the restricted field of view and the fact that no live imaging can be done. On the other hand light microscopy has the advantage of live imaging, following a fluorescently tagged molecule in real time and at lower magnifications the large field of view facilitates the identification and location of sparse individual cells in a large context, e.g., tissue. The combination of these two imaging techniques appears to be a valuable approach to dissect biological events at a submicrometer level. Light microscopy can be used to follow a labelled protein of interest, or a visible organelle such as mitochondria, in time, then the sample is fixed and the exactly same region is investigated by electron microscopy. The time resolution is dependent on the speed of penetration and fixation when chemical fixatives are used and on the reaction time of the operator for cryo-fixation. Light microscopy can also be used to identify cells of interest, e.g., a special cell type in tissue or cells that have been modified by either transfections or RNAi, in a large population of non-modified cells. A further application is to find fluorescence labels in cells on a large section to reduce searching time in the electron microscope. Multiple fluorescence labelling of a series of sections can be correlated with the ultrastructure of the individual sections to get 3D information of the distribution of the marked proteins: array tomography. More and more efforts are put in either converting a fluorescence label into an electron dense product or preserving the fluorescence throughout preparation for the electron microscopy. Here, we will review successful protocols and where possible try to extract common features to better understand the importance of the individual steps in the preparation. Further the new instruments and software, intended to ease correlative light and electron microscopy, are discussed. Last but not least we will detail the approach we have chosen for correlative microscopy.

Use of DNA profiles for investigation using a simulated national DNA database: Part II. Statistical and ethical considerations on familial searching.

Familial searching consists of searching for a full profile left at a crime scene in a National DNA Database (NDNAD). In this paper we are interested in the circumstance where no full match is returned, but a partial match is found between a database member's profile and the crime stain. Because close relatives share more of their DNA than unrelated persons, this partial match may indicate that the crime stain was left by a close relative of the person with whom the partial match was found. This approach has successfully solved important crimes in the UK and the USA. In a previous paper, a model, which takes into account substructure and siblings, was used to simulate a NDNAD. In this paper, we have used this model to test the usefulness of familial searching and offer guidelines for pre-assessment of the cases based on the likelihood ratio. Siblings of "persons" present in the simulated Swiss NDNAD were created. These profiles (N=10,000) were used as traces and were then compared to the whole database (N=100,000). The statistical results obtained show that the technique has great potential confirming the findings of previous studies. However, effectiveness of the technique is only one part of the story. Familial searching has juridical and ethical aspects that should not be ignored. In Switzerland for example, there are no specific guidelines to the legality or otherwise of familial searching. This article both presents statistical results, and addresses criminological and civil liberties aspects to take into account risks and benefits of familial searching.

CleanEx: a database of heterogeneous gene expression data based on a consistent gene nomenclature and linked to an improved annotation system

Résumé: L'automatisation du séquençage et de l'annotation des génomes, ainsi que l'application à large échelle de méthodes de mesure de l'expression génique, génèrent une quantité phénoménale de données pour des organismes modèles tels que l'homme ou la souris. Dans ce déluge de données, il devient très difficile d'obtenir des informations spécifiques à un organisme ou à un gène, et une telle recherche aboutit fréquemment à des réponses fragmentées, voir incomplètes. La création d'une base de données capable de gérer et d'intégrer aussi bien les données génomiques que les données transcriptomiques peut grandement améliorer la vitesse de recherche ainsi que la qualité des résultats obtenus, en permettant une comparaison directe de mesures d'expression des gènes provenant d'expériences réalisées grâce à des techniques différentes. L'objectif principal de ce projet, appelé CleanEx, est de fournir un accès direct aux données d'expression publiques par le biais de noms de gènes officiels, et de représenter des données d'expression produites selon des protocoles différents de manière à faciliter une analyse générale et une comparaison entre plusieurs jeux de données. Une mise à jour cohérente et régulière de la nomenclature des gènes est assurée en associant chaque expérience d'expression de gène à un identificateur permanent de la séquence-cible, donnant une description physique de la population d'ARN visée par l'expérience. Ces identificateurs sont ensuite associés à intervalles réguliers aux catalogues, en constante évolution, des gènes d'organismes modèles. Cette procédure automatique de traçage se fonde en partie sur des ressources externes d'information génomique, telles que UniGene et RefSeq. La partie centrale de CleanEx consiste en un index de gènes établi de manière hebdomadaire et qui contient les liens à toutes les données publiques d'expression déjà incorporées au système. En outre, la base de données des séquences-cible fournit un lien sur le gène correspondant ainsi qu'un contrôle de qualité de ce lien pour différents types de ressources expérimentales, telles que des clones ou des sondes Affymetrix. Le système de recherche en ligne de CleanEx offre un accès aux entrées individuelles ainsi qu'à des outils d'analyse croisée de jeux de donnnées. Ces outils se sont avérés très efficaces dans le cadre de la comparaison de l'expression de gènes, ainsi que, dans une certaine mesure, dans la détection d'une variation de cette expression liée au phénomène d'épissage alternatif. Les fichiers et les outils de CleanEx sont accessibles en ligne (http://www.cleanex.isb-sib.ch/). Abstract: The automatic genome sequencing and annotation, as well as the large-scale gene expression measurements methods, generate a massive amount of data for model organisms. Searching for genespecific or organism-specific information througout all the different databases has become a very difficult task, and often results in fragmented and unrelated answers. The generation of a database which will federate and integrate genomic and transcriptomic data together will greatly improve the search speed as well as the quality of the results by allowing a direct comparison of expression results obtained by different techniques. The main goal of this project, called the CleanEx database, is thus to provide access to public gene expression data via unique gene names and to represent heterogeneous expression data produced by different technologies in a way that facilitates joint analysis and crossdataset comparisons. A consistent and uptodate gene nomenclature is achieved by associating each single gene expression experiment with a permanent target identifier consisting of a physical description of the targeted RNA population or the hybridization reagent used. These targets are then mapped at regular intervals to the growing and evolving catalogues of genes from model organisms, such as human and mouse. The completely automatic mapping procedure relies partly on external genome information resources such as UniGene and RefSeq. The central part of CleanEx is a weekly built gene index containing crossreferences to all public expression data already incorporated into the system. In addition, the expression target database of CleanEx provides gene mapping and quality control information for various types of experimental resources, such as cDNA clones or Affymetrix probe sets. The Affymetrix mapping files are accessible as text files, for further use in external applications, and as individual entries, via the webbased interfaces . The CleanEx webbased query interfaces offer access to individual entries via text string searches or quantitative expression criteria, as well as crossdataset analysis tools, and crosschip gene comparison. These tools have proven to be very efficient in expression data comparison and even, to a certain extent, in detection of differentially expressed splice variants. The CleanEx flat files and tools are available online at: http://www.cleanex.isbsib. ch/.

BlastR--fast and accurate database searches for non-coding RNAs.

We present and validate BlastR, a method for efficiently and accurately searching non-coding RNAs. Our approach relies on the comparison of di-nucleotides using BlosumR, a new log-odd substitution matrix. In order to use BlosumR for comparison, we recoded RNA sequences into protein-like sequences. We then showed that BlosumR can be used along with the BlastP algorithm in order to search non-coding RNA sequences. Using Rfam as a gold standard, we benchmarked this approach and show BlastR to be more sensitive than BlastN. We also show that BlastR is both faster and more sensitive than BlastP used with a single nucleotide log-odd substitution matrix. BlastR, when used in combination with WU-BlastP, is about 5% more accurate than WU-BlastN and about 50 times slower. The approach shown here is equally effective when combined with the NCBI-Blast package. The software is an open source freeware available from www.tcoffee.org/blastr.html.