Delayed Sampling and Automatic Rao-Blackwellization of Probabilistic Programs

We introduce a dynamic mechanism for the solution of analytically-tractable substructure in probabilistic programs, using conjugate priors and affine transformations to reduce variance in Monte Carlo estimators. For inference with Sequential Monte Carlo, this automatically yields improvements such as locally-optimal proposals and Rao-Blackwellization. The mechanism maintains a directed graph alongside the running program that evolves dynamically as operations are triggered upon it. Nodes of the graph represent random variables, edges the analytically-tractable relationships between them. Random variables remain in the graph for as long as possible, to be sampled only when they are used by the program in a way that cannot be resolved analytically. In the meantime, they are conditioned on as many observations as possible. We demonstrate the mechanism with a few pedagogical examples, as well as a linear-nonlinear state-space model with simulated data, and an epidemiological model with real data of a dengue outbreak in Micronesia. In all cases one or more variables are automatically marginalized out to significantly reduce variance in estimates of the marginal likelihood, in the final case facilitating a random-weight or pseudo-marginal-type importance sampler for parameter estimation. We have implemented the approach in Anglican and a new probabilistic programming language called Birch.Comment: 13 pages, 4 figure

Diversities and similarities in PFGE profiles of Campylobacter jejuni isolated from migrating birds and humans

Aims: To genetically sub-type Campylobacter jejuni strains isolated from migratory birds, and to compare these with clinical strains collected in the same area and corresponding time period, with the aim to increase our knowledge on sub-types occurring among wild birds and their possible impact on human disease. Methods and Results: We sub-typed C. jejuni strains from migrating birds (n = 89) and humans (n = 47), using macrorestriction profiling by pulsed-field gel electrophoresis. Isolates from migrant birds often exhibited sub-types with higher levels of similarity to isolates from birds of the same species or feeding guild, than to isolates from other groups of birds. Likewise, could the vast majority of sub-types found among the migrant bird isolates not be identified among sub-types from human cases. Only two bird strains, one from a starling (Sturnus vulgaris) and one from a blackbird (Turdus merula), had sub-types that were similar to some of the human strain sub-types. Conclusions: Isolates from one bird species, or feeding guild, often exhibited high similarities, indicating a common transmission source for individuals, or an association between certain sub-types of C. jejuni and certain ecological guilds or phylogenetic groups of birds. Sub-types occurring among wild birds were in general distinctively different from those observed in patients. The two bird isolates that were similar to human strains were isolated from bird species that often live in close associations with human settlements. Significance and Impact of Study: Wild birds have often been mentioned as a potential route for transmission of C. jejuni to humans. Our study demonstrates that strains isolated from birds most often are different from clinical strains, but that some strain similarities occur, notably in birds strongly associated with human activities

An SNP-Based Linkage Map for Zebrafish Reveals Sex Determination Loci

A surprising diversity of mechanisms controls sex determination of vertebrate organisms, even among closely related species. Both genetic and temperature-dependent systems of sex determination have been described in teleost fish. In the common zebrafish model organism, heteromorphic sex chromosomes are not observed, and the potential role of a genetic component of sex determination remains largely unknown. Here we report a genome-wide linkage study of sex determination in zebrafish using a novel SNP genetic map. We identified loci on zebrafish chromosomes 5 (LOD score 7.9) and 16 (LOD score 9.3) governing sex determination as a complex trait, rather than as an XY or ZW genetic system. Each of these loci contains a prominent candidate gene with a conserved role in sex determination across additional species that suggest potential mechanisms of sex determination in zebrafish. The chromosome 5 locus harbors dmrt1, a key gene in sex determination from fruit flies to humans; mutation of the human DMRT1 ortholog is a cause of complete sex reversal of XY individuals. The chromosome 16 locus harbors cyp21a2; mutation of the human CYP21A2 ortholog is one of the more common causes of pseudohermaphroditism. Mutation detection at each of these candidate genes within the zebrafish cross identified hypomorphic variants on the female-associated allele of each locus. The two loci together accounted for 16% of variance of the trait. Interacting environmental cues are likely to be an additional important component of sex determination in zebrafish

A demonstration of an affinity between pyrite and organic matter in a hydrothermal setting

One of the key-principles of the iron-sulphur world theory is to bring organic molecules close enough to interact with each other, using the surface of pyrite as a substrate in a hydrothermal setting. The present paper explores the relationship of pyrite and organic matter in a hydrothermal setting from the geological record; in hydrothermal calcite veins from Carboniferous limestones in central Ireland. Here, the organic matter is accumulated as coatings around, and through, pyrite grains. Most of the pyrite grains are euhedral-subhedral crystals, ranging in size from ca 0.1-0.5 mm in diameter, and they are scattered throughout the matrix of the vein calcite. The organic matter was deposited from a hydrothermal fluid at a temperature of at least 200°C, and gives a Raman signature of disordered carbon. This study points to an example from a hydrothermal setting in the geological record, demonstrating that pyrite can have a high potential for the concentration and accumulation of organic materials

The point of maximum curvature as a marker for physiological time series

We present a geometric analysis of the model of Stirling. In particular we analyze the curvature of a heart rate time series in response to a step like increment in the exercise intensity. We present solutions for the point of maximum curvature which can be used as a marker of physiological interest. This marker defines the point after which the heart rate no longer continues to rapidly rise and instead follows either a steady state or slow rise. These methods are then applied to find analytic solutions for a mono exponential model which is commonly used in the literature to model the response to a moderate exercise intensity. Numerical solutions are then found for the full model and parameter values presented in Stirling

The consequences of perceived age discrimination amongst older police officers : is social support a buffer ?

This paper considers the possible psychological consequences of perceived agediscrimination, and the possible buffering effect of social support. Findings, based on a studyof perceived age discrimination amongst police officers in the North of England, suggest thatage discrimination acts as a stressor, with officers experiencing negative effects of perceivedage discrimination on job and life satisfaction, perceived power and prestige of the job, andaffective and normative commitment, along with positive effects on withdrawal cognitionsand continuance commitment. For work-based social support, there were positive maineffects on job and satisfaction, power and prestige of the job, and affective and normativecommitment, and a negative main effect on withdrawal cognitions. However, there were nosignificant moderating effects for work-based social support, and we found the anticipatedbuffering effect for non-work-based social support only for life satisfaction, with reversebuffering for job satisfaction and normative commitment. The limitations and implications ofthe study are discussed

NOD × 129.H2g7 Backcross Delineates 129S1/SvImJ-Derived Genomic Regions Modulating Type 1 Diabetes Development in Mice

OBJECTIVE: Introduction of genes targeted in 129/Sv embryonic stem (ES) cells into NOD mice brings about linked genes that may modulate type 1 diabetes. Our objective was to identify 129S1/SvJ non-MHC regions contributing type 1 diabetes resistance or susceptibility in backcross to NOD/LtJ. RESEARCH DESIGN AND METHODS: After congenic transfer of the NOD H2(g7) haplotype onto 129S1/Sv, 310 females were produced by NOD x (NOD x 129.H2(g7))F1 backcross (N2). A genome scan for quantitative trait locus (QTL) affecting clinical diabetes, age of diabetes onset, and insulitis severity was performed using subphenotype characteristics to improve power and resolution for detection of diabetes susceptibility loci. RESULTS: Thirty-six of 310 (11.6%) N2 females developed type 1 diabetes between 14 and 40 weeks. Significant evidence of linkage for only a single previously reported Idd complex locus (Idd10/17/18, chromosome [Chr] 3) was indicated for clinical diabetes. The quantitative traits of insulitis either alone or combined with age at type 1 diabetes onset were significantly linked to known Idd regions on Chr 1 (Idd5 region), Chr 4 (Idd9 region), Chr 8 (Idd22), Chr 11 (Idd4.3), and proximal Chr 17 (Idd16 region). Significant 129S1/Sv resistance contributions were identified on Chr 1, 15 (two loci), and 19, with suggestive evidence for additional novel 129/Sv resistance QTL on Chr 5 and 17 and susceptibility on Chr 2. CONCLUSIONS: The 129S1/SvJ genome harbors collections of both known and potentially novel non-MHC Idd loci. Investigators targeting 129/Sv genes mapping within chromosomal regions reported herein or elsewhere in the genome need to exclude potential contributions from linked Idd loci by generating a NOD.129 control strain expressing the nontargeted allele