On the exponential transform of lemniscates

It is known that the exponential transform of a quadrature domain is a rational function for which the denominator has a certain separable form. In the present paper we show that the exponential transform of lemniscate domains in general are not rational functions, of any form. Several examples are given to illustrate the general picture. The main tool used is that of polynomial and meromorphic resultants.Comment: 19 pages, to appear in the Julius Borcea Memorial Volume, (eds. Petter Branden, Mikael Passare and Mihai Putinar), Trends in Mathematics, Birkhauser Verla

Delivering Behaviour Change Interventions: Development of a Mode of Delivery Ontology [version 1; peer review: 1 approved, 1 approved with reservations]

Background: Investigating and improving the effects of behaviour change interventions requires detailed and consistent specification of all aspects of interventions. An important feature of interventions is the way in which these are delivered, i.e. their mode of delivery. This paper describes an ontology for specifying the mode of delivery of interventions, which forms part of the Behaviour Change Intervention Ontology, currently being developed in the Wellcome Trust funded Human Behaviour-Change Project. / Methods: The Mode of Delivery Ontology was developed in an iterative process of annotating behaviour change interventions evaluation reports, and consulting with expert stakeholders. It consisted of seven steps: 1) annotation of 110 intervention reports to develop a preliminary classification of modes of delivery; 2) open review from international experts (n=25); 3) second round of annotations with 55 reports to test inter-rater reliability and identify limitations; 4) second round of expert review feedback (n=16); 5) final round of testing of the refined ontology by two annotators familiar and two annotators unfamiliar with the ontology; 6) specification of ontological relationships between entities; and 7) transformation into a machine-readable format using the Web Ontology Language (OWL) language and publishing online. / Results: The resulting ontology is a four-level hierarchical structure comprising 65 unique modes of delivery, organised by 15 upper-level classes: Informational, Environmental change, Somatic, Somatic alteration, Individual-based/ Pair-based /Group-based, Uni-directional/Interactional, Synchronous/ Asynchronous, Push/ Pull, Gamification, Arts feature. Relationships between entities consist of is_a. Inter-rater reliability of the Mode of Delivery Ontology for annotating intervention evaluation reports was a=0.80 (very good) for those familiar with the ontology and a= 0.58 (acceptable) for those unfamiliar with it. / Conclusion: The ontology can be used for both annotating and writing behaviour change intervention evaluation reports in a consistent and coherent manner, thereby improving evidence comparison, synthesis, replication, and implementation of effective interventions

Delivering Behaviour Change Interventions: Development of a Mode of Delivery Ontology [version 2; peer review: 2 approved]

Background: Investigating and improving the effects of behaviour change interventions requires detailed and consistent specification of all aspects of interventions. An important feature of interventions is the way in which these are delivered, i.e. their mode of delivery. This paper describes an ontology for specifying the mode of delivery of interventions, which forms part of the Behaviour Change Intervention Ontology, currently being developed in the Wellcome Trust funded Human Behaviour-Change Project. Methods: The Mode of Delivery Ontology was developed in an iterative process of annotating behaviour change interventions evaluation reports, and consulting with expert stakeholders. It consisted of seven steps: 1) annotation of 110 intervention reports to develop a preliminary classification of modes of delivery; 2) open review from international experts (n=25); 3) second round of annotations with 55 reports to test inter-rater reliability and identify limitations; 4) second round of expert review feedback (n=16); 5) final round of testing of the refined ontology by two annotators familiar and two annotators unfamiliar with the ontology; 6) specification of ontological relationships between entities; and 7) transformation into a machine-readable format using the Web Ontology Language (OWL) and publishing online. Results: The resulting ontology is a four-level hierarchical structure comprising 65 unique modes of delivery, organised by 15 upper-level classes: Informational, Environmental change, Somatic, Somatic alteration, Individual-based/ Pair-based /Group-based, Uni-directional/Interactional, Synchronous/ Asynchronous, Push/ Pull, Gamification, Arts feature. Relationships between entities consist of is_a. Inter-rater reliability of the Mode of Delivery Ontology for annotating intervention evaluation reports was a=0.80 (very good) for those familiar with the ontology and a= 0.58 (acceptable) for those unfamiliar with it. Conclusion: The ontology can be used for both annotating and writing behaviour change intervention evaluation reports in a consistent and coherent manner, thereby improving evidence comparison, synthesis, replication, and implementation of effective interventions

Reverse Transcriptase-Coupled Quantitative Real Time PCR Analysis of Cell-Free Transcription on the Chromatin-Assembled p21 Promoter

Background: Cell-free eukaryotic transcription assays have contributed tremendously to the current understanding of the molecular mechanisms that govern transcription at eukaryotic promoters. Currently, the conventional G-less cassette transcription assay is one of the simplest and fastest methods for measuring transcription in vitro. This method requires several components, including the radioisotope labelling of RNA product during the transcription reaction followed by visualization of transcripts using autoradiography. Methodology/Principal Findings: To further simplify and expedite the conventional G-less cassette transcription assay, we have developed a method to incorporate a reverse transcriptase-coupled quantitative real time PCR (RT-qPCR). By using DNA template depletion steps that include DNA template immobilization, Trizol extraction and DNase I treatment, we have successfully enriched p21 promoter-driven transcripts over DNA templates. The quantification results of RNA transcripts using the RT-qPCR assay were comparable to the results of the conventional G-less cassette transcription assay both in naked DNA and chromatin-assembled templates. Conclusions: We first report a proof-of-concept demonstration that incorporating RT-qPCR in cell-free transcription assays can be a simpler and faster alternative method to the conventional radioisotope-mediated transcription assays. This method will be useful for developing high throughput in vitro transcription assays and provide quantitative data for RNA transcript

Development of an Intervention Setting Ontology for behaviour change: Specifying where interventions take place

Background: Contextual factors such as an intervention's setting are key to understanding how interventions to change behaviour have their effects and patterns of generalisation across contexts. The intervention's setting is not consistently reported in published reports of evaluations. Using ontologies to specify and classify intervention setting characteristics enables clear and reproducible reporting, thus aiding replication, implementation and evidence synthesis. This paper reports the development of a Setting Ontology for behaviour change interventions as part of a Behaviour Change Intervention Ontology, currently being developed in the Wellcome Trust funded Human Behaviour-Change Project. Methods: The Intervention Setting Ontology was developed following methods for ontology development used in the Human Behaviour-Change Project: 1) Defining the ontology's scope, 2) Identifying key entities by reviewing existing classification systems (top-down) and 100 published behaviour change intervention reports (bottom-up), 3) Refining the preliminary ontology by literature annotation of 100 reports, 4) Stakeholder reviewing by 23 behavioural science and public health experts to refine the ontology, 5) Assessing inter-rater reliability of using the ontology by two annotators familiar with the ontology and two annotators unfamiliar with it, 6) Specifying ontological relationships between setting entities and 7) Making the Intervention Setting Ontology machine-readable using Web Ontology Language (OWL) and publishing online. Results: The Intervention Setting Ontology consists of 72 entities structured hierarchically with two upper-level classes: Physical setting including Geographic location, Attribute of location (including Area social and economic condition, Population and resource density sub-levels) and Intervention site (including Facility, Transportation and Outdoor environment sub-levels), as well as Social setting. Inter-rater reliability was found to be 0.73 (good) for those familiar with the ontology and 0.61 (acceptable) for those unfamiliar with it. Conclusion: The Intervention Setting Ontology can be used to code information from diverse sources, annotate the setting characteristics of existing intervention evaluation reports and guide future reporting

The impact of low erythrocyte density in human blood on the fitness and energetic reserves of the African malaria vector Anopheles gambiae

Background Anaemia is a common health problem in the developing world. This condition is characterized by a reduction in erythrocyte density, primarily from malnutrition and/or infectious diseases such as malaria. As red blood cells are the primary source of protein for haematophagous mosquitoes, any reduction could impede the ability of mosquito vectors to transmit malaria by influencing their fitness or that of the parasites they transmit. The aim of this study was to determine the impact of differences in the density of red blood cells in human blood on malaria vector (Anopheles gambiae sensu stricto) fitness. The hypotheses tested are that mosquito vector energetic reserves and fitness are negatively influenced by reductions in the red cell density of host human blood meals commensurate with those expected from severe anaemia. Methods Mosquitoes (An. gambiae s.s.) were offered blood meals of different packed cell volume(PCV) of human blood consistent with those arising from severe anaemia (15%) and normalPCV (50%). Associations between mosquito energetic reserves (lipid, glucose and glycogen)and fitness measures (reproduction and survival) and blood meal PCV were investigated. Results The amount of protein that malaria vectors acquired from blood feeding (indexed by haematin excretion) was significantly reduced at low blood PCV. However, mosquitoes feeding on blood of low PCV had the same oviposition rates as those feeding on blood of normal PCV, and showed an increase in egg production of around 15%. The long-term survival of An. gambiae s.s was reduced after feeding on low PCV blood, but PCV had no significant impact on the proportion of mosquitoes surviving through the minimal period required to develop and transmit malaria parasites (estimated as 14 days post-blood feeding). The impact of blood PCV on the energetic reserves of mosquitoes was relatively minor. Conclusions These results suggest that feeding on human hosts whose PCV has been depleted due to severe anaemia does not significantly reduce the fitness or transmission potential of malaria vectors, and indicates that mosquitoes may be able exploit resources for reproduction more efficiently from blood of low rather than normal PCV

Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial

PURPOSE: In the HER2CLIMB study, patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer with brain metastases (BMs) showed statistically significant improvement in progression-free survival (PFS) with tucatinib. We describe exploratory analyses of intracranial efficacy and survival in participants with BMs. PATIENTS AND METHODS: Patients were randomly assigned 2:1 to tucatinib or placebo, in combination with trastuzumab and capecitabine. All patients underwent baseline brain magnetic resonance imaging; those with BMs were classified as active or stable. Efficacy analyses were performed by applying RECIST 1.1 criteria to CNS target lesions by investigator assessment. CNS-PFS (intracranial progression or death) and overall survival (OS) were evaluated in all patients with BMs. Confirmed intracranial objective response rate (ORR-IC) was evaluated in patients with measurable intracranial disease. RESULTS: There were 291 patients with BMs: 198 (48%) in the tucatinib arm and 93 (46%) in the control arm. The risk of intracranial progression or death was reduced by 68% in the tucatinib arm (hazard ratio [HR], 0.32; 95% CI, 0.22 to 0.48; CONCLUSION: In patients with HER2-positive breast cancer with BMs, the addition of tucatinib to trastuzumab and capecitabine doubled ORR-IC, reduced risk of intracranial progression or death by two thirds, and reduced risk of death by nearly half. To our knowledge, this is the first regimen to demonstrate improved antitumor activity against BMs in patients with HER2-positive breast cancer in a randomized, controlled trial

An Age-Structured Extension to the Vectorial Capacity Model

Vectorial capacity and the basic reproductive number (R(0)) have been instrumental in structuring thinking about vector-borne pathogen transmission and how best to prevent the diseases they cause. One of the more important simplifying assumptions of these models is age-independent vector mortality. A growing body of evidence indicates that insect vectors exhibit age-dependent mortality, which can have strong and varied affects on pathogen transmission dynamics and strategies for disease prevention.Based on survival analysis we derived new equations for vectorial capacity and R(0) that are valid for any pattern of age-dependent (or age-independent) vector mortality and explore the behavior of the models across various mortality patterns. The framework we present (1) lays the groundwork for an extension and refinement of the vectorial capacity paradigm by introducing an age-structured extension to the model, (2) encourages further research on the actuarial dynamics of vectors in particular and the relationship of vector mortality to pathogen transmission in general, and (3) provides a detailed quantitative basis for understanding the relative impact of reductions in vector longevity compared to other vector-borne disease prevention strategies.Accounting for age-dependent vector mortality in estimates of vectorial capacity and R(0) was most important when (1) vector densities are relatively low and the pattern of mortality can determine whether pathogen transmission will persist; i.e., determines whether R(0) is above or below 1, (2) vector population growth rate is relatively low and there are complex interactions between birth and death that differ fundamentally from birth-death relationships with age-independent mortality, and (3) the vector exhibits complex patterns of age-dependent mortality and R(0) ∼ 1. A limiting factor in the construction and evaluation of new age-dependent mortality models is the paucity of data characterizing vector mortality patterns, particularly for free ranging vectors in the field

Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P < 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk

An integration of train timetabling, platforming and routing-based cooperative adjustment methodology for dealing with train delay

Train delay is a serious issue that can spread rapidly in the railway network leading to further delay of other trains and detention of passengers in stations. However, the current practice in the event of the trail delay usually depends on train dispatcher's experience, which cannot manage train operation effectively and may have safety risks. The application of intelligent railway monitor and control system can improve train operation management while increasing railway safety. This paper presents a methodology in which train timetabling, platforming and routing models are combined by studying the real-time adjustment and optimization of high speed railway in the case of the train delay in order to produce a cooperative adjustment algorithm so that the train operation adjustment plan can be obtained. MATLAB computer programs have been developed based on the proposed methodology and adjustment criteria have been established from knowledge data bases in order to calculate optimized solutions. A case study is used to demonstrate the proposed methodology. The results show that the proposed method can quickly adjust the train operation plan in the case of the train delay, restore the normal train operation order, and reduce the impact of train delay on railway network effectively and efficiently