Modular analysis of gene expression data with R.

SUMMARY: Large sets of data, such as expression profiles from many samples, require analytic tools to reduce their complexity. The Iterative Signature Algorithm (ISA) is a biclustering algorithm. It was designed to decompose a large set of data into so-called 'modules'. In the context of gene expression data, these modules consist of subsets of genes that exhibit a coherent expression profile only over a subset of microarray experiments. Genes and arrays may be attributed to multiple modules and the level of required coherence can be varied resulting in different 'resolutions' of the modular mapping. In this short note, we introduce two BioConductor software packages written in GNU R: The isa2 package includes an optimized implementation of the ISA and the eisa package provides a convenient interface to run the ISA, visualize its output and put the biclusters into biological context. Potential users of these packages are all R and BioConductor users dealing with tabular (e.g. gene expression) data. AVAILABILITY: http://www.unil.ch/cbg/ISA CONTACT: sven.bergmann@unil.ch

Comparison of indices proposed as criteria for assigning skin notation

OBJECTIVES: Skin notations are used as a hazard identification tool to flag chemicals associated with a potential risk related to transdermal penetration. The transparency and rigorousness of the skin notation assignment process have recently been questioned. We compared different approaches proposed as criteria for these notations as a starting point for improving and systematizing current practice. METHODS: In this study, skin notations, dermal acute lethal dose 50 in mammals (LD(50)s) and two dermal risk indices derived from previously published work were compared using the lists of Swiss maximum allowable concentrations (MACs) and threshold limit values (TLVs) from the American Conference of Governmental Industrial Hygienists (ACGIH). The indices were both based on quantitative structure-activity relationship (QSAR) estimation of transdermal fluxes. One index compared the cumulative dose received through skin given specific exposure surface and duration to that received through lungs following inhalation 8 h at the MAC or TLV. The other index estimated the blood level increase caused by adding skin exposure to the inhalation route at kinetic steady state. Dermal-to-other route ratios of LD(50) were calculated as secondary indices of dermal penetrability. RESULTS: The working data set included 364 substances. Depending on the subdataset, agreement between the Swiss and ACGIH skin notations varied between 82 and 87%. Chemicals with a skin notation were more likely to have higher dermal risk indices and lower dermal LD(50) than chemicals without a notation (probabilities between 60 and 70%). The risk indices, based on cumulative dose and kinetic steady state, respectively, appeared proportional up to a constant independent of chemical-specific properties. They agreed well with dermal LD(50)s (Spearman correlation coefficients -0.42 to -0.43). Dermal-to-other routes LD(50) ratios were moderately associated with QSAR-based transdermal fluxes (Spearman correlation coefficients -0.2 to -0.3). CONCLUSIONS: The plausible but variable relationship between current skin notations and the different approaches tested confirm the need to improve current skin notations. QSAR-based risk indices and dermal toxicity data might be successfully integrated in a systematic alternative to current skin notations for detecting chemicals associated with potential dermal risk in the workplace. [Authors]

Sex-specific selective pressures on body mass in the greater white-toothed shrew, Crocidura russula.

The direction, intensity and shape of viability-, sexual- and fecundity selection on body mass were investigated in a natural population of the greater white-toothed shrew (Crocidura russula), combining parentage assignment through molecular techniques and mark-recapture data over several generations. A highly significant stabilizing viability selection was found in both sexes, presumably stemming from the constraints imposed by their insectivorous habits and high metabolic costs. Sexual selection, directional in both sexes, was twice as large in males than in females. Our results suggest that body mass matters in this context by facilitating the acquisition and defense of a breeding territory. No fecundity selection could be detected. The direction of sexual size dimorphism (SSD) was in agreement with the observed pattern of selective pressures: males were heavier than females, because of stronger sexual selection. SSD intensity, however, was low compared with other mammals, because of the low level of polygyny, the active role of females in territory defense and the intensity of stabilizing viability selection.

Beyond the usual suspects: positive attitudes towards positive symptoms is associated with medication noncompliance in psychosis.

Antipsychotic medication represents the treatment of choice in psychosis according to clinical guidelines. Nevertheless, studies show that half to almost three-quarter of all patients discontinue medication with antipsychotics after some time, a fact which is traditionally ascribed to side-effects, mistrust against the clinician and poor illness insight. The present study investigated whether positive attitudes toward psychotic symptoms (ie, gain from illness) represent a further factor for medication noncompliance. An anonymous online survey was set up in order to prevent conservative response biases that likely emerge in a clinical setting. Following an iterative selection process, data from a total of 113 patients with a likely diagnosis of schizophrenia and a history of antipsychotic treatment were retained for the final analyses (80%). While side-effect profile and mistrust emerged as the most frequent reasons for drug discontinuation, 28% of the sample reported gain from illness (eg, missing voices, feeling of power) as a motive for noncompliance. At least every fourth patient reported the following reasons: stigma (31%), mistrust against the physician/therapist (31%), and rejection of medication in general (28%). Approximately every fifth patient had discontinued antipsychotic treatment because of forgetfulness. On average, patients provided 4 different explanations for noncompliance. Ambivalence toward symptoms and treatment should thoroughly be considered when planning treatment in psychosis. While antipsychotic medication represents the evidence-based cornerstone of the current treatment in schizophrenia, further research is needed on nonpharmacological interventions for noncompliant patients who are willing to undergo intervention but refuse pharmacotherapy.

Cytotaxonomy of Simulium cauchense Floch & Abonnenc and Simulium quadrifidum Lutz (Diptera: Simuliidae) in Brazilian Amazonia

Simulium cauchense Floch & Abonnenc and Simulium quadrifidum Lutz are widely distributed in the Amazon region and are morphologically similar at the larval and pupal stages. Chromosomally, these species are readily distinguished by the position of the nucleolar organizer, which is in the short arm of chromosome I in S. cauchense and in the long arm of chromosomes III in S. quadrifidum. They also differ by three fixed inversions. Sex chromosomes are undifferentiated in both species. Chromosomal resolution of the two species allowed us to evaluate four structural features previously used as diagnostic aids at the larval stage. Characters that distinguish larvae of the two species are the number of branches and branching patterns of the dorsal abdominal setae and the dark band on each primary fan. Branching patterns of the gill histoblasts were often diagnostic, with S. quadrifidum exhibiting more proximal branching and S. cauchense more distal branching. Sites where both species occurred sometimes had larvae with one petiole branching proximally and the other distally; in these cases examination of the chromosomes permitted assignment of the specimen to species. Pigmentation patterns of larvae, on the other hand, are highly variable. Color typically is sex linked in both species.

Construcció d'un SIG de base municipal amb assignació automàtica del nom de carrer a les illes d'habitatges d'una determinada població

Aquest document explica, en els seus diferents capítols, la construcció d'un SIG de base municipal amb assignació automàtica del nom de carrer a les illes d'habitatges d'una determinada població, utilitzant les eines GeoMedia Professional i Visual Basic.

Development of a National English Language Policy and Framework for Legally Resident Adult Immigrants - Horwath Report

The Office of the Minister for Integration (OMI), in conjunction with the Department of Education and Science (DES), commissioned an independent review to assist in the development of a national English Language policy and framework for legally-resident adult immigrants. Horwath Consulting Ireland, in association with Rambll Management and Matrix Knowledge Group, were awarded the contract to undertake this assignment. The terms of reference for the assignment state that: “proposed future developments will be governed by a clear strategy which reflects the importance of English language tuition in overall integration objectives and which addresses key coordination, technical, funding and service-delivery issues."

Self-reported health needs and use of primary health care services by adolescents enrolled in post-mandatory schools or vocational training programmes in Switzerland.

BACKGROUND: The second Swiss Multicenter Adolescent Survey on Health (SMASH02) was conducted among a representative sample (n = 7428) of students and apprentices aged 16 to 20 from the three language areas of Switzerland during the year 2002. This paper reports on health needs expressed by adolescents and their use of health care services over the 12 months preceding the survey. METHODS: Nineteen cantons representing 80% of the resident population agreed to participate. A complex iterative random cluster sample of 600 classes was drawn with classes as primary sampling unit. The participation rate was 97.7% for the classes and 99.8% for the youths in attendance. The self-administered questionnaire included 565 items. The median rate of item non-response was 1.8%. Ethical and legal requirements applying to surveys of adolescent populations were respected. RESULTS: Overall more than 90% of adolescents felt in good to excellent health. Suffering often or very often from different physical complaints or pain was also reported such as headache (boys: 15.9%, girls: 37.4%), stomach-ache (boys: 9.7%, girls: 30.0%), joint pain (boys: 24.7%, girls: 29.5%) or back pain (boys: 24.3%, girls: 34.7%). Many adolescents reported a need for help on psychosocial and lifestyle issues, such as stress (boys: 28.5%, girls: 47.7%) or depression (boys: 18.9%, girls: 34.4%). Although about 75% of adolescents reported having consulted a general practitioner and about one-third having seen another specialist, reported reasons for visits do not correspond to the expressed needs. Less than 10% of adolescents had visited a psychiatrist, a family planning centre or a social worker. CONCLUSIONS: The reported rates of health services utilisation by adolescents does not match the substantial reported needs for help in various areas. This may indicate that the corresponding problems are not adequately detected and/or addressed by professionals from the health and social sectors.

Innovación, financiación y mercados financieros : análisis de las relaciones entre inversión en I+D, estructura de capital y señalización contable

Aquest treball té com a objectiu determinar l'existència de restriccions en el finançament de projectes empresarials de recerca i desenvolupament (R+D) i analitzar-ne les causes. Els resultats de la investigació mostren els fets següents: en primer lloc, hi ha restriccions financeres per a la realització d'inversions en R+D i es manifesten en la necessitat de les empreses de recórrer a recursos interns i a fons aliens a curt termini; en segon lloc, les restriccions esmentades fonamentalment sorgeixen a causa de dos factors, el desequilibri entre les característiques econòmiques de les inversions d'R+D i el comportament dels agents finançadors en els mercats de capitals, i l'existència d'asimetries d'informació entre agents gestors i finançadors; finalment, en tercer lloc, la formulació per part de les empreses de més informació comptable sobre l'R+D desenvolupada comporta la millora de la valoració de l'empresa en els mercats financers i, per tant, l'assignació de fons als processos d'innovació.

The Value of Imperfection : the Wabi-Sabi Principle in Aesthetics and Learning

OER-based learning has the potential to overcome many shortcomings and problems of traditional education. It is not hampered by IP restrictions; can depend on collaborative, cumulative, iterative refinement of resources; and the digital form provides unprecedented flexibility with respect to configuration and delivery. The OER community is a progressive group of educators and learners with decades of learning research to draw from, who know that we must prepare learners for an evolving and diverse reality. Despite this OER tends to replicate the unsuccessful characteristics of traditional education. To remedy this we may need to remember the importance of imperfection, mistakes, problems, disagreement, and the incomplete for engaged learning, and relinquish our notions of perfection, acknowledging that learners learn differently and we need diverse learners. We must stretch our perceptions of quality and provide mechanisms for engaging the incredible pool of educators globally to fulfill the promise of inclusive education.

Evidence evaluation in fingerprint comparison and automated fingerprint identification systems: modeling between finger variability

In the context of the investigation of the use of automated fingerprint identification systems (AFIS) for the evaluation of fingerprint evidence, the current study presents investigations into the variability of scores from an AFIS system when fingermarks from a known donor are compared to fingerprints that are not from the same source. The ultimate goal is to propose a model, based on likelihood ratios, which allows the evaluation of mark-to-print comparisons. In particular, this model, through its use of AFIS technology, benefits from the possibility of using a large amount of data, as well as from an already built-in proximity measure, the AFIS score. More precisely, the numerator of the LR is obtained from scores issued from comparisons between impressions from the same source and showing the same minutia configuration. The denominator of the LR is obtained by extracting scores from comparisons of the questioned mark with a database of non-matching sources. This paper focuses solely on the assignment of the denominator of the LR. We refer to it by the generic term of between-finger variability. The issues addressed in this paper in relation to between-finger variability are the required sample size, the influence of the finger number and general pattern, as well as that of the number of minutiae included and their configuration on a given finger. Results show that reliable estimation of between-finger variability is feasible with 10,000 scores. These scores should come from the appropriate finger number/general pattern combination as defined by the mark. Furthermore, strategies of obtaining between-finger variability when these elements cannot be conclusively seen on the mark (and its position with respect to other marks for finger number) have been presented. These results immediately allow case-by-case estimation of the between-finger variability in an operational setting.

Isolation and characterization of microsatellite loci for the European tree frog (Hyla arborea)

We developed 11 new microsatellite markers for the European tree frog (Hyla arborea), and tested patterns of polymorphism in 54 adults (27 males and 27 females) from two ponds close to Lausanne (Western Switzerland). One marker was sex linked and two pairs displayed linkage disequilibrium. Comparisons of allele numbers with heterozygosity values support a stepwise-mutation model at neutral equilibrium, with mutation rates spanning nearly two orders of magnitude. These markers will prove useful for population genetic studies and fine-scale investigations requiring genetic assignment techniques.

A survey addressing the fundamental matrix estimation problem

Epipolar geometry is a key point in computer vision and the fundamental matrix estimation is the only way to compute it. This article surveys several methods of fundamental matrix estimation which have been classified into linear methods, iterative methods and robust methods. All of these methods have been programmed and their accuracy analysed using real images. A summary, accompanied with experimental results, is given

Cooperation in centralised CATI Household Panel Surveys : A Contact-based Multilevel Analysis to Examine Interviewer, Respondent, and Fieldwork Process Effects

In this research, we analyse the contact-specific mean of the final cooperation probability, distinguishing on the one hand between contacts with household reference persons and with other eligible household members, and on the other hand between first and later contacts. Data comes from two Swiss Household Panel surveys. The interviewer-specific variance is higher for first contacts, especially in the case of the reference person. For later contacts with the reference person, the contact-specific variance dominates. This means that interaction effects and situational factors are decisive. The contact number has negative effects on the performance of contacts with the reference person, positive in the case of other persons. Also time elapsed since the previous contact has negative effects in the case of reference persons. The result of the previous contact has strong effects, especially in the case of the reference person. These findings call for a quick completion of the household grid questionnaire, assigning the best interviewers to conducting the first contact. While obtaining refusals has negative effects, obtaining other contact results has only weak effects on the interviewer's subsequent contact outcome. Using the same interviewer for contacts has no positive effects.

Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma.

PURPOSE: We conducted an international, randomized, phase III trial to evaluate the efficacy and safety of consolidation with yttrium-90 ((90)Y)-ibritumomab tiuxetan in patients with advanced-stage follicular lymphoma in first remission. PATIENTS AND METHODS: Patients with CD20(+) stage III or IV follicular lymphoma, who achieved a complete response (CR)/unconfirmed CR (CRu) or partial response (PR) after first-line induction treatment, were randomly assigned to receive (90)Y-ibritumomab tiuxetan (rituximab 250 mg/m(2) on day -7 and day 0 followed on day 0 by (90)Y-ibritumomab tiuxetan 14.8 MBq/kg; maximum of 1,184 MBq) or no further treatment (control). The primary end point was progression-free survival (PFS), which was calculated from the time of random assignment. RESULTS: A total of 414 patients (consolidation, n = 208; control, n = 206) were enrolled at 77 centers. (90)Y-ibritumomab tiuxetan consolidation significantly prolonged median PFS (after a median observation time of 3.5 years) in all patients (36.5 v 13.3 months in control arm; hazard ratio [HR] = 0.465; P < .0001) and regardless of whether patients achieved PR (29.3 v 6.2 months in control arm; HR = 0.304; P < .0001) or CR/CRu (53.9 v 29.5 months in control arm; HR = 0.613; P = .0154) after induction treatment. Median PFS with consolidation was prolonged in all Follicular Lymphoma International Prognostic Index risk subgroups. After (90)Y-ibritumomab tiuxetan consolidation, 77% of patients in PR after induction converted to CR/CRu, resulting in a final CR rate of 87%. The most common toxicity with (90)Y-ibritumomab tiuxetan was hematologic, and grade 3 or 4 infections occurred in 8% of patients. CONCLUSION: Consolidation of first remission with (90)Y-ibritumomab tiuxetan in advanced-stage follicular lymphoma is highly effective with no unexpected toxicities, prolonging PFS by 2 years and resulting in high PR-to-CR conversion rates regardless of type of first-line induction treatment.