Global and local contributions to the optical specification of time to contact: Observer sensitivity to composite tau

First-order time remaining until a moving observer will pass an environmental element is optically specified in two different ways. The specification provided by global tau (based on the pattern of change of angular bearing) requires that the element is stationary and that the direction of motion is accurately detected, whereas the specification provided by composite tau (based on the patterns of change of optical size and optical distance) does not require either of these. We obtained converging evidence,for our hypothesis. that observers are sensitive to composite tau in four experiments involving, relative judgments of, time to, passage with forced-choice methodology. Discrimination performance was enhanced in the presence of a local expansion component, while being unaffected when the detection of the direction of heading was impaired. Observers relied on the information carried in composite tau rather than on the information carried in its constituent components. Finally, performance was similar under conditions of observer motion and conditions of object motion. Because composite tau specifies first-order time remaining for a large number of situations, the different ways in which it may be detected are discussed.

Analyzing the degree of conflict among belief functions.

The study of alternative combination rules in DS theory when evidence is in conflict has emerged again recently as an interesting topic, especially in data/information fusion applications. These studies have mainly focused on investigating which alternative would be appropriate for which conflicting situation, under the assumption that a conflict is identified. The issue of detection (or identification) of conflict among evidence has been ignored. In this paper, we formally define when two basic belief assignments are in conflict. This definition deploys quantitative measures of both the mass of the combined belief assigned to the emptyset before normalization and the distance between betting commitments of beliefs.We argue that only when both measures are high, it is safe to say the evidence is in conflict. This definition can be served as a prerequisite for selecting appropriate combination rules.

Expressed sequence tag-derived microsatellites for the cool-water marine copepod Calanus finmarchicus

The copepod Calanus finmarchicus is the major contributor to zooplankton biomass in the North Atlantic and Norwegian Sea, but recent studies have shown a 70% decrease in abundance as well as a northward shift in the species' range. Insights into dispersal capabilities gained from population genetic studies will be crucial in predicting the response of C. finmarchicus communities to climate change and, consequently, we have developed a set of expressed sequence tag-derived microsatellite markers to allow fine-scale elucidation of population structuring and dispersal. Ten polymorphic markers displayed between two and 19 alleles, with levels of expected heterozygosity ranging from 0.044 to 0.924.

A Census-based longitudinal study of variations in survival amongst residents of nursing and residential homes in Northern Ireland

Background: despite the intensive services provided to residents of care homes, information on death rates is not routinely available for this population in the UK. Objective: to quantify mortality rates across the care home population of Northern Ireland, and assess variation by type of care home and resident characteristics. Design: a prospective, Census-based cohort study, with 5-year follow-up. Participants: all 9,072 residents of care homes for people aged 65 and over at the time of the 2001 census with a special emphasis on the 2,112 residents admitted during the year preceding census day. Measurements: age, sex, self-reported health, marital status, residence (not in care home, residential home, dual registered home, nursing home), elderly mentally infirm care provision. Results: the median survival among nursing home residents was 2.33 years (95% CI 2.25–2.59), for dual registered homes 2.75 (95% CI 2.42–3.17) and for residential homes 4.51 (95% CI 3.92–4.92) years. Age, sex and self-reported health showed weaker associations in the sicker populations in nursing homes compared to those in residential care or among the non-institutionalised. Conclusions: the high mortality in care homes indicates that places in care homes are reserved for the most severely ill and dependent. Death rates may not be an appropriate care quality measure for this population, but may serve as a useful adjunct for clinical staff and the planning of care home provision.

Perceptions of exercise among people who have not attended cardiac rehabilitation following myocardial infarction.

Perceptions of exercise among nonattenders of cardiac rehabilitation (CR) were explored using semistructured interviews. Analysis indicated that participants did not recognize the cardiovascular benefits of exercise, and perceived keeping
active through daily activities as sufficient for health. Health professionals were perceived to downplay the importance of exercise and CR, and medication was viewed as being more important than exercise for promoting health. The content of CR programmes and the benefits of exercise need to be further explained to patients post-MI, and in a manner that communicates to patients that these programmes are valued by significant others, particularly health professionals.

Acculturation and religion in schools: the views of young people from minority belief backgrounds

This paper aims to explore the relationship between religious identity, acculturation strategies and perceptions of acculturation orientation in the school context amongst young people from minority
belief backgrounds. Based on a qualitative study including interviews with 26 young people from religious minority belief backgrounds in Northern Ireland, it is argued that acculturation theory provides a useful lens for understanding how young people from religious minority belief backgrounds navigate majority religious school contexts. Using a qualitative approach to explore acculturation theory enables an in-depth understanding of the inter-relationship between minority belief youth’s acculturation strategies and their respective school contexts. Similar to previous research, integrationist attitudes generally prevailed amongst minority belief young people in this study. The findings highlight how young people negotiate their religious identities in a complex web of inter-relationships between their minority religious belief community and the mainstream school culture as represented through peer and staff attitudes, school ethos and practices and religious education. Young people demonstrated differentiated understandings of acculturation orientations within the school context, which they evaluated on the basis of complex perceptions of educational policy, interpersonal relationships and individuals’ motivations. Findings are discussed in view of acculturation tensions, which arose particularly in relation to the religious education curriculum and their implications for opt-out provision as stipulated by human rights law.

Application of a mechanobiological simulation technique to stents used clinically

Many cardiovascular diseases are characterised by the restriction of blood flow through arteries. Stents can be expanded within arteries to remove such restrictions; however, tissue in-growth into the stent can lead to restenosis. In order to predict the long-term efficacy of stenting, a mechanobiological model of the arterial tissue reaction to stress is required. In this study, a computational model of arterial tissue response to stenting is applied to three clinically relevant stent designs. We ask the question whether such a mechanobiological model can differentiate between stents used clinically, and we compare these predictions to a purely mechanical analysis. In doing so, we are testing the hypothesis that a mechanobiological model of arterial tissue response to injury could predict the long-term outcomes of stent design. Finite element analysis of the expansion of three different stent types was performed in an idealised, 3D artery. Injury was calculated in the arterial tissue using a remaining-life damage mechanics approach. The inflammatory response to this initial injury was modelled using equations governing variables which represented tissue-degrading species and growth factors. Three levels of inflammation response were modelled to account for inter-patient variability. A lattice-based model of smooth muscle cell behaviour was implemented, treating cells as discrete agents governed by local rules. The simulations predicted differences between stent designs similar to those found in vivo. It showed that the volume of neointima produced could be quantified, providing a quantitative comparison of stents. In contrast, the differences between stents based on stress alone were highly dependent on the choice of comparison criteria. These results show that the choice of stress criteria for stent comparisons is critical. This study shows that mechanobiological modelling may provide a valuable tool in stent design, allowing predictions of their long-term efficacy. The level of inflammation was shown to affect the sensitivity of the model to stent design. If this finding was verified in patients, this could suggest that high-inflammation patients may require alternative treatments to stenting.

The Interlaboratory Robustness Of Next-Generation Sequencing (IRON) Study Phase II: Deep-Sequencing Analyses Of Hematological Malignancies Performed In 8,867 Cases By An International Network Involving 27 Laboratories

Introduction: Amplicon deep-sequencing using second-generation sequencing technology is an innovative molecular diagnostic technique and enables a highly-sensitive detection of mutations. As an international consortium we had investigated previously the robustness, precision, and reproducibility of 454 amplicon next-generation sequencing (NGS) across 10 laboratories from 8 countries (Leukemia, 2011;25:1840-8).

Aims: In Phase II of the study, we established distinct working groups for various hematological malignancies, i.e. acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), and multiple myeloma. Currently, 27 laboratories from 13 countries are part of this research consortium. In total, 74 gene targets were selected by the working groups and amplicons were developed for a NGS deep-sequencing assay (454 Life Sciences, Branford, CT). A data analysis pipeline was developed to standardize mutation interpretation both for accessing raw data (Roche Amplicon Variant Analyzer, 454 Life Sciences) and variant interpretation (Sequence Pilot, JSI Medical Systems, Kippenheim, Germany).

Results: We will report on the design, standardization, quality control aspects, landscape of mutations, as well as the prognostic and predictive utility of this assay in a cohort of 8,867 cases. Overall, 1,146 primer sequences were designed and tested. In detail, for example in AML, 924 cases had been screened for CEBPA mutations. RUNX1 mutations were analyzed in 1,888 cases applying the deep-sequencing read counts to study the stability of such mutations at relapse and their utility as a biomarker to detect residual disease. Analyses of DNMT3A (n=1,041) were focused to perform landscape investigations and to address the prognostic relevance. Additionally, this working group is focusing on TET2, ASXL1, and TP53 analyses. A novel prognostic model is being developed allowing stratification of AML into prognostic subgroups based on molecular markers only. In ALL, 1,124 pediatric and adult cases have been screened, including 763 assays for TP53 mutations both at diagnosis and relapse of ALL. Pediatric and adult leukemia expert labs developed additional content to study the mutation incidence of other B and T lineage markers such as IKZF1, JAK2, IL7R, PAX5, EP300, LEF1, CRLF2, PHF6, WT1, JAK1, PTEN, AKT1, IL7R, NOTCH1, CREBBP, or FBXW7. Further, the molecular landscape of CLL is changing rapidly. As such, a separate working group focused on analyses including NOTCH1, SF3B1, MYD88, XPO1, FBXW7 and BIRC3. Currently, 922 cases were screened to investigate the range of mutational burden of NOTCH1 mutations for their prognostic relevance. In MDS, RUNX1 mutation analyses were performed in 977 cases. The prognostic relevance of TP53 mutations in MDS was assessed in additional 327 cases, including isolated deletions of chromosome 5q. Next, content was developed targeting genes of the cellular splicing component, e.g. SF3B1, SRSF2, U2AF1, and ZRSR2. In BCR-ABL1-negative MPN, nine genes of interest (JAK2, MPL, TET2, CBL, KRAS, EZH2, IDH1, IDH2, ASXL1) have been analyzed in a cohort of 155 primary myelofibrosis cases searching for novel somatic mutations and addressing their relevance for disease progression and leukemia transformation. Moreover, an assay was developed and applied to CMML cases allowing the simultaneous analysis of 25 leukemia-associated target genes in a single sequencing run using just 20 ng of starting DNA. Finally, nine laboratories are studying CML, applying ultra-deep sequencing of the BCR-ABL1 tyrosine kinase domain. Analyses were performed on 615 cases investigating the dynamics of expansion of mutated clones under various tyrosine kinase inhibitor therapies.

Conclusion: Molecular characterization of hematological malignancies today requires high diagnostic sensitivity and specificity. As part of the IRON-II study, a network of laboratories analyzed a variety of disease entities applying amplicon-based NGS assays. Importantly, the consortium not only standardized assay design for disease-specific panels, but also achieved consensus on a common data analysis pipeline for mutation interpretation. Distinct working groups have been forged to address scientific tasks and in total 8,867 cases had been analyzed thus far.

A simple bioanalytical method for the quantification of antiepileptic drugs in dried blood spots

An increasing number of publications on the dried blood spot (DBS) sampling approach for the quantification of drugs and metabolites have been spurred on by the inherent advantages of this sampling technique. In the present research, a selective and sensitive high-performance liquid chromatography method for the concurrent determination of multiple antiepileptic drugs (AEDs) [levetiracetam (LVT), lamotrigine (LTG), phenobarbital (PHB)], carbamazepine (CBZ) and its active metabolite carbamazepine-10,11 epoxide (CBZE)] in a single DBS has been developed and validated. Whole blood was spotted onto Guthrie cards and dried. Using a standard punch (6. mm diameter), a circular disc was punched from the card and extracted with methanol: acetonitrile (3:1, v/v) containing hexobarbital (Internal Standard) and sonicated prior to evaporation. The extract was then dissolved in water and vortex mixed before undergoing solid phase extraction using HLB cartridges. Chromatographic separation of the AEDs was achieved using Waters XBridge™ C18 column with a gradient system. The developed method was linear over the concentration ranges studied with r=0.995 for all compounds. The lower limits of quantification (LLOQs) were 2, 1, 2, 0.5 and 1. µg/mL for LVT, LTG, PHB, CBZE and CBZ, respectively. Accuracy (%RE) and precision (%CV) values for within and between day were

Transmission Potential of Rift Valley Fever virus over the course of the 2010 epidemic in South Africa

A Rift Valley fever (RVF) epidemic affecting animals on domestic livestock farms was reported in South Africa during January-August 2010. The first cases occurred after heavy rainfall, and the virus subsequently spread countrywide. To determine the possible effect of environmental conditions and vaccination on RVF virus transmissibility, we estimated the effective reproduction number (R) for the virus over the course of the epidemic by extending the Wallinga and Teunis algorithm with spatial information. Re reached its highest value in mid-February and fell below unity around mid-March, when vaccination coverage was 7.5%-45.7% and vector-suitable environmental conditions were maintained. The epidemic fade-out likely resulted first from the immunization of animals following natural infection or vaccination. The decline in vector-suitable environmental conditions from April onwards and further vaccination helped maintain R below unity. Increased availability of vaccine use data would enable evaluation of the effect of RVF vaccination campaigns.

Attention during social interaction in children with autism: Comparison to specific language impairment, typical development, and links to cognition

Eye-tracking studies have shown how people with autism spend significantly less time looking at socially relevant information on-screen compared to those developing typically. This has been suggested to impact on the development of socio-cognitive skills in autism. We present novel evidence of how attention atypicalities in children with autism extend to real-life interaction, in comparison to typically developing (TD) children and children with specific language impairment (SLI). We explored the allocation of attention during social interaction with an interlocutor, and how aspects of attention (awareness checking) related to traditional measures of social cognition (false belief attribution). We found divergent attention allocation patterns across the groups in relation to social cognition ability. Even though children with autism and SLI performed similarly on the socio- cognitive tasks, there were syndrome-specific atypicalities of their attention patterns. Children with SLI were most similar to TD children in terms of prioritising attention to socially pertinent information (eyes, face, awareness checking). Children with autism showed reduced attention to the eyes and face, and slower awareness checking. This study provides unique and timely insight into real-world social gaze (a)typicality in autism, SLI and typical development, its relationship to socio-cognitive ability, and raises important issues for intervention.