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Accessibility of adolescent health services.

Adolescents represent a large proportion of the population. As they mature and become sexually active, they face more serious health risks. Most face these risks with too little factual information, too little guidance about sexual responsibility and multiple barriers to accessing health care. A typical descriptive and explanatory design was used to determine what the characteristics of an accessible adolescent health service should be. Important results and conclusions that were reached indicate that the adolescent want a medical doctor and a registered nurse to be part of the health team treating them and they want to be served in the language of their choice. Family planning, treatment of sexually transmitted diseases and psychiatric services for the prevention of suicide are services that should be included in an adolescent accessible health service. The provision of health education concerning sexual transmitted diseases and AIDS is a necessity. The service should be available thought out the week (included Saturdays) and within easy reach. It is recommended that minor changes in existing services be made, that will contribute towards making a health delivery service an adolescent accessible service. An adolescent accessible health service can in turn make a real contribution to the community's efforts to improve the health of its adolescents and can prove to be a rewarding professional experience to the health worker.

Adolescent↗

Spatial working memory score of humans in a large radial maze, similar to published score of rats, implies capacity close to the magical number 7 +/- 22.

To compare the working memory (WM) capacity of humans to rats, we tested humans with a 17-arm radial maze and, in a follow up experiment, with a 13-arm radial maze. Both mazes were 15.2 meters in diameter, painted on a grassy field. In one version of the 13-arm experiment, we required a concurrent nonsense vocalization to impede subjects' use of language to remember locations. Subjects were instructed to choose arms of the radial maze unsystematically--as rats generally appear to do--and to visit the end of each arm only once. In additional procedures, we tested working memory capacity in a verbal task that is more analogous to the radial maze than is the typical ordered recall test. Subjects were asked to try to recite a sequence of 17 numbers (i.e., 18 through 34) or letters (A through Q) in unsystematic order, with no repeats. In another experiment subjects recited 13 numbers (14-26) or letters (A-M). In all tests, subjects were allowed only as many responses as there were distinct items (17 or 13, respectively). Average correct-response (nonrepeat) scores were 14.4 for the 17-arm maze and 14.1 for both of the verbal 17-item tests; these scores are close to the reported score for rats in a 17-arm radial maze. Average scores were between 10.8 and 11.4 in all of the 13-item maze and recitation tasks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Genome-wide prediction, display and refinement of binding sites with information theory-based models.

BACKGROUND: We present Delila-genome, a software system for identification, visualization and analysis of protein binding sites in complete genome sequences. Binding sites are predicted by scanning genomic sequences with information theory-based (or user-defined) weight matrices. Matrices are refined by adding experimentally-defined binding sites to published binding sites. Delila-Genome was used to examine the accuracy of individual information contents of binding sites detected with refined matrices as a measure of the strengths of the corresponding protein-nucleic acid interactions. The software can then be used to predict novel sites by rescanning the genome with the refined matrices. RESULTS: Parameters for genome scans are entered using a Java-based GUI interface and backend scripts in Perl. Multi-processor CPU load-sharing minimized the average response time for scans of different chromosomes. Scans of human genome assemblies required 4-6 hours for transcription factor binding sites and 10-19 hours for splice sites, respectively, on 24- and 3-node Mosix and Beowulf clusters. Individual binding sites are displayed either as high-resolution sequence walkers or in low-resolution custom tracks in the UCSC genome browser. For large datasets, we applied a data reduction strategy that limited displays of binding sites exceeding a threshold information content to specific chromosomal regions within or adjacent to genes. An HTML document is produced listing binding sites ranked by binding site strength or chromosomal location hyperlinked to the UCSC custom track, other annotation databases and binding site sequences. Post-genome scan tools parse binding site annotations of selected chromosome intervals and compare the results of genome scans using different weight matrices. Comparisons of multiple genome scans can display binding sites that are unique to each scan and identify sites with significantly altered binding strengths. CONCLUSIONS: Delila-Genome was used to scan the human genome sequence with information weight matrices of transcription factor binding sites, including PXR/RXRalpha, AHR and NF-kappaB p50/p65, and matrices for RNA binding sites including splice donor, acceptor, and SC35 recognition sites. Comparisons of genome scans with the original and refined PXR/RXRalpha information weight matrices indicate that the refined model more accurately predicts the strengths of known binding sites and is more sensitive for detection of novel binding sites.

Binding Sites↗

The role of aminoglycosides in combination with a beta-lactam for the treatment of bacterial endocarditis: a meta-analysis of comparative trials.

BACKGROUND: The addition of an aminoglycoside to a beta-lactam for the treatment of patients with infective endocarditis has been supported by data from laboratory and animal studies. PURPOSE: We sought to review the evidence from the available comparative clinical trials regarding the role of aminoglycosides in combination with a beta-lactam for the treatment of bacterial endocarditis caused by Gram-positive cocci. DATA SOURCES: The studies for our meta-analysis were retrieved from searches of the PubMed and Cochrane Central Register of Controlled Trials databases, as well as from the references cited in relevant articles. No limits were set regarding the language and date of publication of the studies. STUDY SELECTION: Included studies were prospective studies that provided comparative data regarding the effectiveness of the treatment and/or mortality in patients receiving monotherapy with a beta-lactam or beta-lactam/aminoglycoside combination therapy. DATA EXTRACTION: Two independent reviewers performed the literature search, study selection and extraction of data from relevant studies. DATA SYNTHESIS: No clinical trial comparing beta-lactam monotherapy with beta-lactam/aminoglycoside combination therapy for the treatment of enterococcal endocarditis was found. We performed a meta-analysis of five available comparative trials [four randomized controlled trials (RCTs) and one comparative prospective trial], which included 261 patients with bacterial endocarditis in native valves due to Staphylococcus aureus (four studies) or streptococci of the viridans group (one study). There was no statistically significant difference between beta-lactam monotherapy and beta-lactam/aminoglycoside combination therapy regarding mortality [odds ratio (OR) = 0.59, 95% confidence interval (95% CI) = 0.21-1.66], treatment success (OR = 1.25, 95% CI = 0.49-3.05), treatment success without surgery (OR = 1.66, 95% CI = 0.64-4.30) or relapse of endocarditis (OR = 0.79, 95% CI = 0.15-4.29). Nephrotoxicity was less common in the beta-lactam monotherapy arm than in the beta-lactam/aminoglycoside combination therapy arm (OR = 0.38, 95% CI = 0.16-0.88, P = 0.024). No difference between the two treatment arms was found in subanalyses of the four studies that included only patients with staphylococcal infections in terms of mortality (OR = 0.69, 95% CI = 0.26-1.86, fixed effects model), treatment success (OR = 1.27, 95% CI = 0.47-3.43, fixed effects model) or relapse (OR = 0.76, 95% CI = 0.12-4.92, fixed effects model). LIMITATIONS: The relatively small number of available comparative trials was the major limitation of this meta-analysis. CONCLUSIONS: The limited evidence from the available prospective comparative studies does not offer support for the addition of an aminoglycoside to beta-lactam treatment of patients with endocarditis caused by Gram-positive cocci. A large multicentre RCT is necessary to reach a definitive conclusion on this issue.

Aminoglycosides↗

Neonatal resuscitation training program in Malaysia: results of the first 2 years.

OBJECTIVES: To determine the number of providers and instructors trained by the initial 37 core instructors during the first 2 years following the launch of the Malaysian Neonatal Resuscitation Program (NRP). To identify remediable problems which interfered with the propagation of the NRP in Malaysia. METHODOLOGY: A prospective observational study carried out over a 2-year period between 2 September 1996 to 2 September 1998. For every training course conducted, the instructors completed a NRP course report form (Form A) that documented the instructors involved in the course. For every participant who attended the course and successfully completed it, the instructors submitted a record form (Form B) that contained the name, hospital address, department, profession, place of work, language used for training and the marks obtained by the individual participant. After each course, completed forms A and B were returned to the NRP secretariat for compilation. RESULTS: Of the 37 core instructors, 35 (94.6%) carried out training courses in their respective home states. A further 513 new instructors and 2256 providers were trained subsequently. A total of 2806 health personnel from all 13 states of Malaysia were NRP-certified during the first 2 years. However, 61.2% (n = 335) of the 550 instructors were inactive trainers, having trained less than four personnel per instructor a year. Most of the NRP-certified personnel were either doctors (32.0%) or nursing staff (64.4%). More than 60% of these worked either in the labour rooms, neonatal intensive care units or special care nurseries. At least one person from all three university hospitals and all general hospitals, 89.3% (92/103) of the district hospitals, 3.5% (73/2090) of the maternal and child health services, and 21% (46/219) of the private hospitals and maternity homes, were trained in the NRP. CONCLUSION: Dissemination of the NRP in Malaysia during the first 2 years was very encouraging. Further efforts should be made to spread the program to private hospitals and the maternal and child health services. In view of the large number of inactive instructors, the criteria for future selection of instructors should be more stringent.

Cohort Studies↗

Genomic analysis of regulatory network dynamics reveals large topological changes.

Network analysis has been applied widely, providing a unifying language to describe disparate systems ranging from social interactions to power grids. It has recently been used in molecular biology, but so far the resulting networks have only been analysed statically. Here we present the dynamics of a biological network on a genomic scale, by integrating transcriptional regulatory information and gene-expression data for multiple conditions in Saccharomyces cerevisiae. We develop an approach for the statistical analysis of network dynamics, called SANDY, combining well-known global topological measures, local motifs and newly derived statistics. We uncover large changes in underlying network architecture that are unexpected given current viewpoints and random simulations. In response to diverse stimuli, transcription factors alter their interactions to varying degrees, thereby rewiring the network. A few transcription factors serve as permanent hubs, but most act transiently only during certain conditions. By studying sub-network structures, we show that environmental responses facilitate fast signal propagation (for example, with short regulatory cascades), whereas the cell cycle and sporulation direct temporal progression through multiple stages (for example, with highly inter-connected transcription factors). Indeed, to drive the latter processes forward, phase-specific transcription factors inter-regulate serially, and ubiquitously active transcription factors layer above them in a two-tiered hierarchy. We anticipate that many of the concepts presented here--particularly the large-scale topological changes and hub transience--will apply to other biological networks, including complex sub-systems in higher eukaryotes.

Algorithms↗

Stratus not altocumulus: a new view of the yeast protein interaction network.

Systems biology approaches can reveal intermediary levels of organization between genotype and phenotype that often underlie biological phenomena such as polygenic effects and protein dispensability. An important conceptualization is the module, which is loosely defined as a cohort of proteins that perform a dedicated cellular task. Based on a computational analysis of limited interaction datasets in the budding yeast Saccharomyces cerevisiae, it has been suggested that the global protein interaction network is segregated such that highly connected proteins, called hubs, tend not to link to each other. Moreover, it has been suggested that hubs fall into two distinct classes: "party" hubs are co-expressed and co-localized with their partners, whereas "date" hubs interact with incoherently expressed and diversely localized partners, and thereby cohere disparate parts of the global network. This structure may be compared with altocumulus clouds, i.e., cotton ball-like structures sparsely connected by thin wisps. However, this organization might reflect a small and/or biased sample set of interactions. In a multi-validated high-confidence (HC) interaction network, assembled from all extant S. cerevisiae interaction data, including recently available proteome-wide interaction data and a large set of reliable literature-derived interactions, we find that hub-hub interactions are not suppressed. In fact, the number of interactions a hub has with other hubs is a good predictor of whether a hub protein is essential or not. We find that date hubs are neither required for network tolerance to node deletion, nor do date hubs have distinct biological attributes compared to other hubs. Date and party hubs do not, for example, evolve at different rates. Our analysis suggests that the organization of global protein interaction network is highly interconnected and hence interdependent, more like the continuous dense aggregations of stratus clouds than the segregated configuration of altocumulus clouds. If the network is configured in a stratus format, cross-talk between proteins is potentially a major source of noise. In turn, control of the activity of the most highly connected proteins may be vital. Indeed, we find that a fluctuation in steady-state levels of the most connected proteins is minimized.

Computational Biology↗

Investigating the generators of the scalp recorded visuo-verbal P300 using cortically constrained source localization.

Considerable ambiguity exists about the generators of the scalp recorded P300, despite a vast body of research employing a diverse range of methodologies. Previous investigations employing source localization techniques have been limited largely to equivalent current dipole models, with most studies identifying medial temporal and/or hippocampal sources, but providing little information about the contribution of other cortical regions to the generation of the scalp recorded P3. Event-related potentials (ERPs) were recorded from 5 subjects using a 124-channel sensor array during the performance of a visuo-verbal Oddball task. Cortically constrained, MRI-guided boundary element modeling was used to identify the cortical generators of this target P3 in individual subjects. Cortical generators of the P3 were localized principally to the intraparietal sulcus (IPS) and surrounding superior parietal lobes (SPL) bilaterally in all subjects, though with some variability across subjects. Two subjects also showed activity in the lingual/inferior occipital gyrus and mid-fusiform gyrus. A group cortical surface was calculated by non-linear warping of each subject's segmented cortex followed by averaging and creation of a group mesh. Source activity identified across the group reflected the individual subject activations in the IPS and SPL bilaterally and in the lingual/inferior occipital gyrus primarily on the left. Activation of IPS and SPL is interpreted to reflect the role of this region in working memory and related attention processes and visuo-motor integration. The activity in left lingual/inferior occipital gyrus is taken to reflect activation of regions associated with modality-specific analysis of visual word forms.

Adult↗

The HUPO PSI's molecular interaction format--a community standard for the representation of protein interaction data.

A major goal of proteomics is the complete description of the protein interaction network underlying cell physiology. A large number of small scale and, more recently, large-scale experiments have contributed to expanding our understanding of the nature of the interaction network. However, the necessary data integration across experiments is currently hampered by the fragmentation of publicly available protein interaction data, which exists in different formats in databases, on authors' websites or sometimes only in print publications. Here, we propose a community standard data model for the representation and exchange of protein interaction data. This data model has been jointly developed by members of the Proteomics Standards Initiative (PSI), a work group of the Human Proteome Organization (HUPO), and is supported by major protein interaction data providers, in particular the Biomolecular Interaction Network Database (BIND), Cellzome (Heidelberg, Germany), the Database of Interacting Proteins (DIP), Dana Farber Cancer Institute (Boston, MA, USA), the Human Protein Reference Database (HPRD), Hybrigenics (Paris, France), the European Bioinformatics Institute's (EMBL-EBI, Hinxton, UK) IntAct, the Molecular Interactions (MINT, Rome, Italy) database, the Protein-Protein Interaction Database (PPID, Edinburgh, UK) and the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING, EMBL, Heidelberg, Germany).

Database Management Systems↗

From computing with numbers to computing with words. From manipulation of measurements to manipulation of perceptions.

Interest in issues relating to consciousness has grown markedly during the last several years. And yet, nobody can claim that consciousness is a well-understood concept that lends itself to precise analysis. It may be argued that, as a concept, consciousness is much too complex to fit into the conceptual structure of existing theories based on Aristotelian logic and probability theory. An approach suggested in this paper links consciousness to perceptions and perceptions to their descriptors in a natural language. In this way, those aspects of consciousness which relate to reasoning and concept formation are linked to what is referred to as the methodology of computing with words (CW). Computing, in its usual sense, is centered on manipulation of numbers and symbols. In contrast, computing with words, or CW for short, is a methodology in which the objects of computation are words and propositions drawn from a natural language (e.g., small, large, far, heavy, not very likely, the price of gas is low and declining, Berkeley is near San Francisco, it is very unlikely that there will be a significant increase in the price of oil in the near future, etc.). Computing with words is inspired by the remarkable human capability to perform a wide variety of physical and mental tasks without any measurements and any computations. Familiar examples of such tasks are parking a car, driving in heavy traffic, playing golf, riding a bicycle, understanding speech, and summarizing a story. Underlying this remarkable capability is the brain's crucial ability to manipulate perceptions--perceptions of distance, size, weight, color, speed, time, direction, force, number, truth, likelihood, and other characteristics of physical and mental objects. Manipulation of perceptions plays a key role in human recognition, decision and execution processes. As a methodology, computing with words provides a foundation for a computational theory of perceptions: a theory which may have an important bearing on how humans make--and machines might make--perception-based rational decisions in an environment of imprecision, uncertainty, and partial truth. A basic difference between perceptions and measurements is that, in general, measurements are crisp, whereas perceptions are fuzzy. One of the fundamental aims of science has been and continues to be that of progressing from perceptions to measurements. Pursuit of this aim has led to brilliant successes. We have sent men to the moon; we can build computers that are capable of performing billions of computations per second; we have constructed telescopes that can explore the far reaches of the universe; and we can date the age of rocks that are millions of years old. But alongside the brilliant successes stand conspicuous underachievements and outright failures. We cannot build robots that can move with the agility of animals or humans; we cannot automate driving in heavy traffic; we cannot translate from one language to another at the level of a human interpreter; we cannot create programs that can summarize non-trivial stories; our ability to model the behavior of economic systems leaves much to be desired; and we cannot build machines that can compete with children in the performance of a wide variety of physical and cognitive tasks. It may be argued that underlying the underachievements and failures is the unavailability of a methodology for reasoning and computing with perceptions rather than measurements. An outline of such a methodology--referred to as a computational theory of perceptions--is presented in this paper. The computational theory of perceptions (CTP) is based on the methodology of CW. In CTP, words play the role of labels of perceptions, and, more generally, perceptions are expressed as propositions in a natural language. CW-based techniques are employed to translate propositions expressed in a natural language into what is called the Generalized Constraint Language (GCL). In this language, the meaning of a proposition is expressed as a generalized constraint, X isr R, where X is the constrained variable, R is the constraining relation, and isr is a variable copula in which r is an indexing variable whose value defines the way in which R constrains X. Among the basic types of constraints are possibilistic, veristic, probabilistic, random set, Pawlak set, fuzzy graph, and usuality. The wide variety of constraints in GCL makes GCL a much more expressive language than the language of predicate logic. In CW, the initial and terminal data sets, IDS and TDS, are assumed to consist of propositions expressed in a natural language. These propositions are translated, respectively, into antecedent and consequent constraints. Consequent constraints are derived from antecedent constraints through the use of rules of constraint propagation. The principal constraint propagation rule is the generalized extension principle. (ABSTRACT TRUNCATED)

Consciousness↗

Management of facial nerve injury due to temporal bone trauma.

OBJECTIVE: This article provides an overview of relevant data regarding the management of facial nerve injury due to temporal bone trauma. DATA SOURCES: Sources used were relevant English language clinical and basic science publications. STUDY SELECTION: A Medline search dating back to 1966 for articles concerning temporal bone trauma and facial nerve injury including both human and animal data was performed. Articles were included if they contained relevant data or were significant reviews on the subject. A retrograde bibliography search was then conducted to acquire any articles that may have been missed by the computerized search, including those papers published prior to 1966. DATA EXTRACTION: The data from each paper were reviewed individually. DATA SYNTHESIS: The data were not amenable to formal meta-analysis or valid data summarization. CONCLUSIONS: Patients who should not require surgical intervention include those who have: documented normal facial nerve function after injury regardless of progression, presentation with incomplete facial nerve paralysis with no progression to complete paralysis, and degeneration <95% on ENoG. The remaining patients presumably have a poorer prognosis for return of facial nerve function although it remains unclear exactly how poor the return of function will be. Decompression surgery likely has a beneficial effect if performed within 14 days of injury, so those patients with expected poor natural outcomes may be offered this intervention. Late decompression surgery is not recommended. Late exploratory surgery is recommended only in those patients who do not experience adequate recovery of facial nerve function and likely require nerve repair. Despite the availability of a relatively large volume of published data, there remain many unanswered questions.

Algorithms↗

The effects on priming of word frequency, number of repetitions, and delay depend on the magnitude of priming.

Conflicting findings with respect to the effects of experimental manipulations on priming have been reported in previous studies. It is argued that, in many priming tasks, large amounts of task-relevant information are available from various sources, and that, therefore, the information available from a specific study episode will have only a small impact on overall performance level. Under such circumstances, high levels of baseline performance and small priming effects will be observed. The experiments reported here investigated the hypothesis that a high baseline performance in information-processing tasks that are used to measure priming may constrain priming effects. In a series of word-naming experiments, perceptual difficulty and, therefore, baseline performance was manipulated. Under easy conditions, priming effects were relatively small and were not affected by word frequency, spaced repetition, or delay. Under more difficult conditions, priming effects were larger, and significant effects of all of the above-mentioned experimental manipulations were observed. Under conditions that produced the largest priming effects, a significant relationship between priming and explicit-memory performance could be observed. In the last experiment, it was shown that the characteristics of the retrieval task can substantially affect the magnitude of priming. It is argued that priming effects should be considered to reflect interactions between memory traces and the information-processing components of the priming task.

Cognition↗

The organization of memory. A parallel distributed processing perspective.

Parallel distributed processing (PDP) provides a contemporary framework for thinking about the nature and organization of perception, memory, language, and thought. In this talk I describe the overall framework briefly and discuss its implications of procedural, semantic, and episodic memory. According to the PDP approach, the processing of information takes place through the interaction of a large number of simple processing units organized into modules. Storage occurs through the modification of connection weights based on the system's response to its input, that provides an opportunity for incremental storage. I will describe how connection modification may give rise through the course of experience to procedural learning and to the formation of semantic memories, structured by their semantic content. I will argue that the discovery of semantic structure requires gradual learning, with repeated exposure to representative samples of the structure to be learned. I will then describe two neuropsychological implications of the PDP approach. First, I will consider the possible modular organization of semantic information in the brain. Then, I will examine the role of the hippocampus in learning and memory. In the first case, we will see how the PDP approach leads us to see how brain damage might produce apparent dissociations between categories, when in fact the underlying organization is not by category but by modality. In the second case, we will see that the PDP approach gives us a new way to understand why it is important that unique, arbitrary associations not be stored all at once in the same memory's systems used for semantic information.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

Bio++: a set of C++ libraries for sequence analysis, phylogenetics, molecular evolution and population genetics.

BACKGROUND: A large number of bioinformatics applications in the fields of bio-sequence analysis, molecular evolution and population genetics typically share input/output methods, data storage requirements and data analysis algorithms. Such common features may be conveniently bundled into re-usable libraries, which enable the rapid development of new methods and robust applications. RESULTS: We present Bio++, a set of Object Oriented libraries written in C++. Available components include classes for data storage and handling (nucleotide/amino-acid/codon sequences, trees, distance matrices, population genetics datasets), various input/output formats, basic sequence manipulation (concatenation, transcription, translation, etc.), phylogenetic analysis (maximum parsimony, markov models, distance methods, likelihood computation and maximization), population genetics/genomics (diversity statistics, neutrality tests, various multi-locus analyses) and various algorithms for numerical calculus. CONCLUSION: Implementation of methods aims at being both efficient and user-friendly. A special concern was given to the library design to enable easy extension and new methods development. We defined a general hierarchy of classes that allow the developer to implement its own algorithms while remaining compatible with the rest of the libraries. Bio++ source code is distributed free of charge under the CeCILL general public licence from its website http://kimura.univ-montp2.fr/BioPP.

Algorithms↗

Biochemical systems theory: operational differences among variant representations and their significance.

An appropriate language or formalism for the analysis of complex biochemical systems has been sought for several decades. The necessity for such a formalism results from the large number of interacting components in biochemical systems and the complex non-linear character of these interactions. The Power-Law Formalism, an example of such a language, underlies several recent attempts to develop an understanding of integrated biochemical systems. It is the simplest representation of integrated biochemical systems that has been shown to be consistent with well-known growth laws and allometric relationships--the most regular, quantitative features that have been observed among the systemic variables of complex biochemical systems. The Power-Law Formalism provides the basis for Biochemical Systems Theory, which includes several different strategies of representation. Among these, the synergistic-system (S-system) representation is the most useful, as judged by a variety of objective criteria. This paper first describes the predominant features of the S-system representation. It then presents detailed comparisons between the S-system representation and other variants within Biochemical Systems Theory. These comparisons are made on the basis of objective criteria that characterize the efficiency, power, clarity and scope of each representation. Two of the variants within Biochemical Systems Theory are intimately related to other approaches for analyzing biochemical systems, namely Metabolic Control Theory and Flux-Oriented Theory. It is hoped that the comparisons presented here will result in a deeper understanding of the relationships among these variants. Finally, some recent developments are described that demonstrate the potential for further growth of Biochemical Systems Theory and the underlying Power-Law Formalism on which it is based.

Animals↗

Interpretation of bodily symptoms in hypochondriasis.

Although it has been suggested that hypochondriasis is caused by the misinterpretation of innocuous bodily sensations, support for this hypothesis rests largely upon uncontrolled self-report. We investigated the interpretation of ambiguous bodily sensations in three experiments using separate samples of non-clinical subjects differing in level of hypochondriacal concern. Results confirmed that subjects with high hypochondriacal concern endorse more thoughts about illness interpretations of bodily sensations, but reported thought content resembled 'catastrophic' rather than the 'non-emergency' thoughts suggested by Warwick and Salkovskis (Hypochondriasis. Behavior Research and Therapy, 28, 105-117, 1990). Presence of an interpretive bias was further supported in a study of recognition bias for disambiguated versions of ambiguously threatening sentences, although this applied as much to social as to illness threats. A final experiment failed to support the hypothesis of an automatic inference bias, but did show that subjects with high hypochondriacal concern were quicker to correctly identify previously exposed illness words. Thus, reported thoughts are consistent with catastrophic interpretations of common bodily sensations, but interpretive bias may not be limited to illness threat. However, high hypochondriacal subjects do show a more specific enhanced perceptual sensitivity to illness cues, which may play a role in maintaining their concern with bodily symptoms.

Adolescent↗

Event-related fMRI for the suppression of speech-associated artifacts in stuttering.

The purpose of this study was to establish functional magnetic resonance imaging (fMRI) for the investigation of brain function during overt speech production in stuttering. Up to now this technique has rarely been used for the investigation of speech production paradigms because artifacts related to overt speaking largely impair the sensitivity toward task-related activation. Recently, the temporal delay of the hemodynamic response has been exploited to achieve a suppression of speech-related artifacts. By the limitation to very short utterances (one word), a temporal segregation of the respective effects was accomplished by means of an event-related experimental design. However, the investigation of speech production in persons who stutter requires a more extensive speaking situation. Since longer and more complex utterances evoke more symptoms of stuttering than reading of single words, a useful task should at least include the reading of full sentences. In this study we performed simulations to investigate the correlation of speech-related artifacts with the respective hemodynamic response in dependency on speech duration and rate of data sampling. Furthermore, we show that prolonged stimulus durations and repetition times of 3 s still allow an effective suppression of speech-related artifacts in fluent as well as in nonfluent speakers. Not only were obvious false activations at high contrast cerebrospinal fluid tissue borders widely eliminated, subjects also displayed consistent activation in speech-related and motor areas. As these results widely resemble those obtained by earlier neuroimaging studies on language production, event-related fMRI seems to be capable of recording neurophysiological correlates of overt speech production.

Adult↗

Clustering short time series gene expression data.

MOTIVATION: Time series expression experiments are used to study a wide range of biological systems. More than 80% of all time series expression datasets are short (8 time points or fewer). These datasets present unique challenges. On account of the large number of genes profiled (often tens of thousands) and the small number of time points many patterns are expected to arise at random. Most clustering algorithms are unable to distinguish between real and random patterns. RESULTS: We present an algorithm specifically designed for clustering short time series expression data. Our algorithm works by assigning genes to a predefined set of model profiles that capture the potential distinct patterns that can be expected from the experiment. We discuss how to obtain such a set of profiles and how to determine the significance of each of these profiles. Significant profiles are retained for further analysis and can be combined to form clusters. We tested our method on both simulated and real biological data. Using immune response data we show that our algorithm can correctly detect the temporal profile of relevant functional categories. Using Gene Ontology analysis we show that our algorithm outperforms both general clustering algorithms and algorithms designed specifically for clustering time series gene expression data. AVAILABILITY: Information on obtaining a Java implementation with a graphical user interface (GUI) is available from http://www.cs.cmu.edu/~jernst/st/ SUPPLEMENTARY INFORMATION: Available at http://www.cs.cmu.edu/~jernst/st/

Algorithms↗