Follow-up question handling in the IMIX and Ritel systems: A comparative study

One of the basic topics of question answering (QA) dialogue systems is how follow-up questions should be interpreted by a QA system. In this paper, we shall discuss our experience with the IMIX and Ritel systems, for both of which a follow-up question handling scheme has been developed, and corpora have been collected. These two systems are each other's opposites in many respects: IMIX is multimodal, non-factoid, black-box QA, while Ritel is speech, factoid, keyword-based QA. Nevertheless, we will show that they are quite comparable, and that it is fruitful to examine the similarities and differences. We shall look at how the systems are composed, and how real, non-expert, users interact with the systems. We shall also provide comparisons with systems from the literature where possible, and indicate where open issues lie and in what areas existing systems may be improved. We conclude that most systems have a common architecture with a set of common subtasks, in particular detecting follow-up questions and finding referents for them. We characterise these tasks using the typical techniques used for performing them, and data from our corpora. We also identify a special type of follow-up question, the discourse question, which is asked when the user is trying to understand an answer, and propose some basic methods for handling it

Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients.

PurposeMany women with an elevated risk of hereditary breast and ovarian cancer have previously tested negative for pathogenic mutations in BRCA1 and BRCA2. Among them, a subset has hereditary susceptibility to cancer and requires further testing. We sought to identify specific groups who remain at high risk and evaluate whether they should be offered multi-gene panel testing.MethodsWe tested 300 women on a multi-gene panel who were previously enrolled in a long-term study at UCSF. As part of their long-term care, all previously tested negative for mutations in BRCA1 and BRCA2 either by limited or comprehensive sequencing. Additionally, they met one of the following criteria: (i) personal history of bilateral breast cancer, (ii) personal history of breast cancer and a first or second degree relative with ovarian cancer, and (iii) personal history of ovarian, fallopian tube, or peritoneal carcinoma.ResultsAcross the three groups, 26 women (9%) had a total of 28 pathogenic mutations associated with hereditary cancer susceptibility, and 23 women (8%) had mutations in genes other than BRCA1 and BRCA2. Ashkenazi Jewish and Hispanic women had elevated pathogenic mutation rates. In addition, two women harbored pathogenic mutations in more than one hereditary predisposition gene.ConclusionsAmong women at high risk of breast and ovarian cancer who have previously tested negative for pathogenic BRCA1 and BRCA2 mutations, we identified three groups of women who should be considered for subsequent multi-gene panel testing. The identification of women with multiple pathogenic mutations has important implications for family testing

A decision analysis approach for optimal groundwater monitoring system design under uncertainty

International audienceGroundwater contamination is the degradation of the natural quality of groundwater as a result of human activity. Landfills are one of the most common human activities threatening the groundwater quality. The objective of the monitoring systems is to detect the contaminant plumes before reaching the regulatory compliance boundary in order to prevent the severe risk to both society and groundwater quality, and also to enable cost-effective counter measures in case of a failure. The detection monitoring problem typically has a multi-objective nature. A multi-objective decision model (called MONIDAM) which links a classic decision analysis approach with a stochastic simulation model is applied to determine the optimal groundwater monitoring system given uncertainties due to the hydrogeological conditions and contaminant source characteristics. A Monte Carlo approach is used to incorporate uncertainties. Hydraulic conductivity and the leak location are the random inputs of the simulation model. The design objectives considered in the model are: (1) maximizing the detection probability, (2) minimizing the contaminated area and, (3) minimize the total cost of the monitoring system. The results show that the monitoring systems located close to the source are optimal except for the cases with very high unit installation and sampling cost and/or very cheap unit remediation cost

Vitamin D intake in Australian adults and the modeled effects of milk and breakfast cereal fortification

Objective: Vitamin D intake from foods or supplements is a safe and attractive means to improve vitamin D status of populations. The aim of this study was to help identify population subgroups that would benefit most from efforts to increase intake. To do so, we investigated which personal characteristics are associated with vitamin D intake in an Australian population and modeled possible effects of expanded food fortification practices. Methods: We investigated vitamin D intake in a population-based random sample of 785 adults, using a validated food frequency questionnaire, and assessed associations with personal and behavioral characteristics. We identified vitamin D food sources and modeled the hypothetical effects of blanket fortification of milk and breakfast cereals. Results: Average total vitamin D intake was 4.4 (±4.0) μg/g and below adequate intake for most participants in all age and sex subgroups. Higher intake was associated with being female, having a serious medical condition, energy intake below the median, and vitamin D supplement use (all P < 0.05). The "meat, fish, and eggs" food group contributed most to total vitamin D intake (51%), followed by dairy products and related foods (43%). If all milk and breakfast cereals were to be fortified with vitamin D, the average intake of vitamin D from foods would increase from 3.6 (±2.4) μg/d to 6.3 (±3.2) μg/d, with similar increases in all age and sex subgroups. Conclusions: Vitamin D intake in Australia is generally below recommended levels, and few personal characteristics help to identify subgroups with low intake. Blanket vitamin D fortification of milk and breakfast cereals would substantially increase average vitamin D intake in Australian adults of all ages

Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells

Stem cell factor (SCF) has an important role in the proliferation, differentiation, survival, and migration of hematopoietic cells. SCF exerts its effects by binding to cKit, a receptor with intrinsic tyrosine kinase activity. Activation of phosphatidylinositol 3'-kinase (PI3-K) by cKit was previously shown to contribute to many SCF-induced cellular responses. Therefore, PI3-K-dependent signaling pathways activated by SCF were investigated. The PI3-K-dependent activation and phosphorylation of the tyrosine kinase Tec and the adapter molecule p62Dok-1 are reported. The study shows that Tec and Dok-1 form a stable complex with Lyn and 2 unidentified phosphoproteins of 56 and 140 kd. Both the Tec homology and the SH2 domain of Tec were identified as being required for the interaction with Dok-1, whereas 2 domains in Dok-1 appeared to mediate the association with Tec. In addition, Tec and Lyn were shown to phosphorylate Dok-1, whereas phosphorylated Dok-1 was demonstrated to bind to the SH2 domains of several signaling molecules activated by SCF, including Abl, CrkL, SHIP, and PLCgamma-1, but not those of Vav and Shc. These findings suggest that p62Dok-1 may function as an important scaffold molecule in cKit-mediated signaling

‘Together … for only a moment’ British newspaper constructions of altruistic non-commercial surrogate motherhood

Objectives: To explore how national altruistic surrogacy is framed in a representative selection of the British press. Methods: A study of 90 British national newspaper articles was carried out using the Lexis-Nexis data base to search for articles on altruistic surrogacy. Content analysis of gain, loss, neutral frames and high or low alarm and vulnerability frames in the titles and the body of the text was carried out. The type of construction used in the article content was also analysed. Data were coded and consensus reached using a coding strategy specifically developed for the purposes of this study. Results: Titles and content were predominantly loss, high alarm and high vulnerability framed. The content was also gain framed, and written with a focus on the social and legal aspects differentially between the newspaper types. Discussion: The tabloid press emphasizes social issues, and the middle market and serious press focus on legal issues of altruistic surrogacy. Selectively framed and reinforced information provided by the different newspapers, reflect the different readership, with Tabloid readers likely to be, surrogates (mostly from lower socioeconomic strata) and serious/ middle-market readers likely to be commissioning parents (mostly professionals)

Functional C-terminally Encoded Peptide (CEP) plant hormone domains evolved de novo in the plant parasite Rotylenchulus reniformis

This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and The James Hutton Institute through a PhD studentship to SE-vdA. The James Hutton Institute receives funding from the Scottish Government Rural and Environment Science and Analytical Services division. SE-vdA is supported by BBSRC grant BB/M014207/1.Sedentary Plant-Parasitic Nematodes (PPNs) induce and maintain an intimate relationship with their host, stimulating cells adjacent to root vascular tissue to re-differentiate into unique and metabolically active “feeding sites”. The interaction between PPNs and their host is mediated by nematode effectors. We describe the discovery of a large and diverse family of effector genes, encoding C-terminally Encoded Peptide (CEP) plant hormone mimics (RrCEPs), in the syncytia-forming plant-parasite Rotylenchulus reniformis. The particular attributes of RrCEPs distinguish them from all other CEPs, regardless of origin. Together with the distant phylogenetic relationship of R. reniformis to the only other CEP-encoding nematode genus identified to date (Meloidogyne), this suggests CEPs likely evolved de novo in R. reniformis. We have characterised the first member of this large gene family (RrCEP1), demonstrating its significant upregulation during the plant-nematode interaction and expression in the effector-producing pharyngeal gland cell. All internal CEP domains of multi-domain RrCEPs are followed by di-basic residues, suggesting a mechanism for cleavage. A synthetic peptide corresponding to RrCEP1 domain 1 is biologically active and capable of upregulating plant nitrate transporter (AtNRT2.1) expression, while simultaneously reducing primary root elongation. When a non-CEP containing, syncytia-forming PPN species (Heterodera schachtii) infects Arabidopsis in a CEP-rich environment a smaller feeding site is produced. We hypothesise that CEPs of R. reniformis represent a two-fold adaptation to sustained biotrophy in this species; 1) increasing host nitrate uptake while 2) limiting the size of the syncytial feeding site produced.Publisher PDFPeer reviewe

Expectations and experiences of gamete donors and donor-conceived adults searching for genetics relatives using DNA linking through a voluntary register

STUDY QUESTION: What are the experiences of donor-conceived adults and donors who are searching for a genetic link through the use of a DNA-based voluntary register service? SUMMARY ANSWER: Donor-conceived adults and donors held positive beliefs about their search and although some concerns in relation to finding a genetically linked relative were reported, these were not a barrier to searching. WHAT IS KNOWN ALREADY: Research with donor-conceived people has consistently identified their interest in learning about-and in some cases making contact with-their donor and other genetic relatives. However, donor-conceived individuals or donors rarely have the opportunity to act on these desires. STUDY DESIGN, SIZE, AND DURATION: A questionnaire was administered for online completion using Bristol Online Surveys. The survey was live for 3 months and responses were collected anonymously. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: The survey was completed by 65 donor-conceived adults, 21 sperm donors and 5 oocyte donors who had registered with a DNA-based voluntary contact register in the UK. The questionnaire included socio-demographic questions, questions specifically developed for the purposes of this study and the standardized Aspects of Identity Questionnaire (AIQ). MAIN RESULTS AND THE ROLE OF CHANCE: Motivations for searching for genetic relatives were varied, with the most common reasons being curiosity and passing on information. Overall, participants who were already linked and those awaiting a link were positive about being linked and valued access to a DNA-based register. Collective identity (reflecting self-defining feelings of continuity and uniqueness), as assessed by the AIQ, was significantly lower for donor-conceived adults when compared with the donor groups (P 0.05) for donor-conceived adults. LIMITATIONS, REASONS FOR CAUTION: Participants were members of a UK DNA-based registry which is unique. It was therefore not possible to determine how representative participants were of those who did not register for the service, those in other countries or of those who do not seek information exchange or contact. WIDER IMPLICATIONS OF THE FINDINGS: This is the first survey exploring the experiences of donor-conceived adults and donors using a DNA-based voluntary register to seek information about and contact with genetic relatives and the first to measure aspects of identity using standardized measures. Findings provide valuable information about patterns of expectations and experiences of searching through DNA linking, identity and of having contact in the context of donor conception that will inform future research, practice and policy development

A qualitative exploration of health-related quality of life and health behaviours in children with sickle cell disease and healthy siblings

Objectives This study explored the health-related quality of life (HRQL) and health behaviours of children with sickle cell disease (SCD) and healthy siblings, drawing on Gap theory, which suggests HRQL is the discrepancy between current and ideal selves. Design Thirty-two interviews, facilitated by children’s drawings of their current and ideal selves were thematically analysed. Results Two themes were identified. First, limitations of SCD and adjusted expectations. Children with SCD report some discrepancy in HRQL as they would like to participate in more physical activity, but overall, they appear to have normalised their condition and adjusted their expectations in the context of the limits of their condition. Healthy siblings worry about their sibling and have greater expectations about engaging in adventurous activities and for their future. Second, coping with SCD. Children have limited social support, although children with SCD seek support from their mothers. They also modify health behaviours, like reducing exercise to help prevent and cope with sickle-related pain. Conclusion Children have some discrepancies in their HRQL but adjusted expectations among children with SCD may reduce discrepancy. Adapting health behaviours may help to cope with SCD but it is important that reductions in physical activity do not impair HRQL

Exploring health-related quality of life, exercise and alcohol use in adolescents with sickle cell disease and healthy siblings

Objective This study explored the health-related quality of life (HRQL) and health behaviours of adolescents with sickle cell disease (SCD) and healthy siblings, drawing on Gap theory which suggests HRQL is the discrepancy between current and ideal selves. Design Twenty-three adolescents with SCD and 21 healthy siblings aged 13 to 17 years participated in eight focus groups. Results Thematic analysis identified three themes: learning to accept SCD, coping with SCD and influences on health behaviours. Adolescents appear to have normalised and adapted to SCD. Adolescents with SCD have learnt effective coping strategies, such as moderating engagement in exercise. Unlike heathy siblings, they were not encouraged to exercise by parents but were content with their level of participation. Both groups were influenced to exercise by role models or wanting to socialise, and influenced to drink alcohol by peers, but there was limited understanding of the potential negative impacts of alcohol on SCD. Conclusion There does not appear to be a discrepancy between adolescents’ current and ideal selves, providing optimism about their HRQL. Further consideration of engaging in healthy behaviours is needed, but it is important to strike a balance so that modifications to lifestyle do not impair HRQL