Multivariate Hierarchical Frameworks for Modelling Delayed Reporting in Count Data

In many fields and applications count data can be subject to delayed reporting. This is where the total count, such as the number of disease cases contracted in a given week, may not be immediately available, instead arriving in parts over time. For short term decision making, the statistical challenge lies in predicting the total count based on any observed partial counts, along with a robust quantification of uncertainty. In this article we discuss previous approaches to modelling delayed reporting and present a multivariate hierarchical framework where the count generating process and delay mechanism are modelled simultaneously. Unlike other approaches, the framework can also be easily adapted to allow for the presence of under-reporting in the final observed count. To compare our approach with existing frameworks, one of which we extend to potentially improve predictive performance, we present a case study of reported dengue fever cases in Rio de Janeiro. Based on both within-sample and out-of-sample posterior predictive model checking and arguments of interpretability, adaptability, and computational efficiency, we discuss the advantages and disadvantages of each modelling framework.Comment: Biometrics (2019

A theoretical and semiemprical correction to the long-range dispersion power law of stretched graphite

In recent years intercalated and pillared graphitic systems have come under increasing scrutiny because of their potential for modern energy technologies. While traditional \emph{ab initio} methods such as the LDA give accurate geometries for graphite they are poorer at predicting physicial properties such as cohesive energies and elastic constants perpendicular to the layers because of the strong dependence on long-range dispersion forces. `Stretching' the layers via pillars or intercalation further highlights these weaknesses. We use the ideas developed by [J. F. Dobson et al, Phys. Rev. Lett. {\bf 96}, 073201 (2006)] as a starting point to show that the asymptotic $C_3 D^{-3}$ dependence of the cohesive energy on layer spacing $D$ in bigraphene is universal to all graphitic systems with evenly spaced layers. At spacings appropriate to intercalates, this differs from and begins to dominate the $C_4 D^{-4}$ power law for dispersion that has been widely used previously. The corrected power law (and a calculated $C_3$ coefficient) is then unsuccesfully employed in the semiempirical approach of [M. Hasegawa and K. Nishidate, Phys. Rev. B {\bf 70}, 205431 (2004)] (HN). A modified, physicially motivated semiempirical method including some $C_4 D^{-4}$ effects allows the HN method to be used successfully and gives an absolute increase of about $2-3$ to the predicted cohesive energy, while still maintaining the correct $C_3 D^{-3}$ asymptotics

Deriving Information Requirements from Responsibility Models

This paper describes research in understanding the requirements for complex information systems that are constructed from one or more generic COTS systems. We argue that, in these cases, behavioural requirements are largely defined by the underlying system and that the goal of the requirements engineering process is to understand the information requirements of system stakeholders. We discuss this notion of information requirements and propose that an understanding of how a socio-technical system is structured in terms of responsibilities is an effective way of discovering this type of requirement. We introduce the idea of responsibility modelling and show, using an example drawn from the domain of emergency planning, how a responsibility model can be used to derive information requirements for a system that coordinates the multiple agencies dealing with an emergency

Nonuniversality of the dispersion interaction: analytic benchmarks for van der Waals energy functionals

We highlight the non-universality of the asymptotic behavior of dispersion forces, such that a sum of inverse sixth power contributions is often inadequate. We analytically evaluate the cross-correlation energy Ec between two pi-conjugated layers separated by a large distance D within the electromagnetically non-retarded Random Phase Approximation, via a tight-binding model. For two perfect semimetallic graphene sheets at T=0K we find Ec = C D^{-3}, in contrast to the "insulating" D^{-4} dependence predicted by currently accepted approximations. We also treat the case where one graphene layer is replaced by a thin metal, a model relevant to the exfoliation of graphite. Our general considerations also apply to nanotubes, nanowires and layered metals.Comment: 4 pages, 0 fig

Tracking endogenous and grafted neural progenitor cells in normal and ischaemic brains using MRI contrast agents and genetic labelling

Cerebral ischaemia is a major cause of mortality and morbidity globally. Neural stem and progenitor cells (NPC) have the potential to contribute to brain repair and regeneration after an ischaemic event. Both endogenous and grafted NPC have been shown to migrate towards the ischaemic lesion, and differentiate into neurons. This thesis investigates methods of labeling and tracking the migration neural progenitor cells to a site of cerebral ischaemic injury, using magnetic resonance imaging (MRI) contrast agents and transgenic lineage tracing techniques. First, labeling of exogenous NPC populations was investigated, for use in cell tracking in grafting studies. Cell labeling was optimized in vitro with fetal NPC using the iron oxide-based MRI contrast agent. A labeling method was developed using the FePro contrast agent, which maximized iron oxide uptake, was non-toxic to NPC, and did not interfere with NPC proliferation and differentiation. Labelled cells were then grafted into the brain after cerebral ischaemia, and imaged over four weeks using MRI. NPC migration was not observed in vivo, but an endogenous contrast evolved over time within the lesioned tissue, which presented a source of confounding signal for cell tracking. Endogenous ferric iron was observed in the lesion on histological sections. Several limitations of using MRI-based iron oxide contrast agents were highlighted in this study. To circumvent these limitations, we considered the development of gadolinium-based MRI contrast agents for cellular labeling and tracking, in collaboration with Imperial College chemistry department. Polymeric Gd-DOTA chelates were synthesized and designed for maximal r1 relaxivity, and their relaxivity and effects on cell viability were assessed. Through this approach, we identified a number of candidate polymeric Gd-DOTA chelates with high relaxivity and low cytotoxicity for use in cellular imaging and tracking studies. Next, cell tracking of endogenous NPC was investigated, using MRI contrast agent and transgenic lineage tracing approaches. A method of in situ labeling of endogenous NPC with the MRI contrast agent FePro was developed. NPC were labeled with FePro in situ, and their normal migration to the olfactory bulb, where they contribute to neurogenesis, could be imaged in vivo and ex vivo. In a second study, the migration of NPC constitutively expressing green fluorescent protein (GPF) under the promoters of genes of two developmentally distinct cortical and striatal NPC populations, was investigated following cerebral ischaemia. Both cortical and striatal populations of NPC were observed to contribute to the migrating streams of NPC that were observed in the striatum after five weeks post-ischaemia. These studies demonstrate that MRI contrast agents offer the potential for in vivo, longitudinal tracking of NPC migration, in both grafted and endogenous NPC populations. Coupled with transgenic lineage tracing, and used in animal models of CNS injury such as cerebral ischaemia, labeling and tracking the migration of NSC with MRI contrast agents can contribute to our understanding of NPC biology in pathological environments

Enhanced dispersion interaction between quasi-one dimensional conducting collinear structures

Recent investigations have highlighted the failure of a sum of $R^{-6}$ terms to represent the dispersion interaction in parallel metallic, anisotropic, linear or planar nanostructures [J. F. Dobson, A. White, and A. Rubio, Phys. Rev. Lett. 96, 073201 (2006) and references therein]. By applying a simple coupled plasmon approach and using electron hydrodynamics, we numerically evaluate the dispersion (non-contact van der Waals) interaction between two conducting wires in a collinear pointing configuration. This case is compared to that of two insulating wires in an identical geometry, where the dispersion interaction is modelled both within a pairwise summation framework, and by adding a pinning potential to our theory leading to a standard oscillator-type model of insulating dielectric behavior. Our results provide a further example of enhanced dispersion interaction between two conducting nanosystems compared to the case of two insulating ones. Unlike our previous work, this calculation explores a region of relatively close coupling where, although the electronic clouds do not overlap, we are still far from the asymptotic region where a single power law describes the dispersion energy. We find that strong differences in dispersion attraction between metallic and semiconducting / insulating cases persist into this non-asymptotic region. While our theory will need to be supplemented with additional short-ranged terms when the electronic clouds overlap, it does not suffer from the short-distance divergence exhibited by purely asymptotic theories, and gives a natural saturation of the dispersion energy as the wires come into contact.Comment: 10 pages, 5 figures. Added new extended numerical calculations, new figures, extra references and heavily revised tex

Synthesis of cubic diamond in the graphite-magnesium carbonate and graphite-K2Mg(CO3)(2) systems at high pressure of 9-10 GPa region

Cubic diamond was synthesized with two systems, (1) graphite with pure magnesium carbonate (magnesite) and (2) graphite with mixed potassium and magnesium carbonate at pressures and temperatures above 9.5 GPa, 1600 degrees C and 9 GPa, 1650 degrees C, respectively. At these conditions (1) the pure magnesite is solid, whereas (2) the mixed carbonate exists as a melt. In this pressure range, graphite seems to be partially transformed into hexagonal diamond. Measured carbon isotope delta(13)C values for all the materials suggest that the origin of the carbon source to form cubic diamond was the initial graphite powder, and not the carbonates

Mesoscale monitoring of the soil freeze/thaw boundary from orbital microwave radiometry

The fundamental objectives are to test the feasibility of delineating the lateral boundary between frozen and thawed condition in the surface layer of soil from orbital microwave radiometry and secondly to examine the sensitivity of general circulation models to an explicit parameterization of the boundary condition. Physical models were developed to relate emissivity to scene properties and a simulation package was developed to predict brightness temperature as a function of emissivity and physical temperature in order to address issues of heterogeneity, scaling, and scene dynamics. Radiative transfer models were develped for both bare soil surfaces and those obscured by an intervening layer of vegetation or snow. These models relate the emissivity to the physical properties of the soil and to those of the snow or vegetation cover. A SMMR simulation package was developed to evaluate the adequacy of the emission models and the limiting effects of scaling for realistic scenarios incorporating spatially heterogeneous scenes with dynamic moisture and temperature gradients at the pixel scale

Nuclear Organization in Breast Cancer: A Dissertation

The nuclear matrix (NM) is a fibrogranular network of ribonucleoproteins upon which transcriptional complexes and regulatory genomic sequences are organized. A hallmark of cancer is the disorganization of nuclear architecture; however, the extent to which the NM is involved in malignancy is not well studied. The RUNX1 and RUNX2 proteins form complexes within the NM to promote hematopoiesis and osteoblastogenesis, respectively at the transcriptional level. RUNX1 and RUNX2 are both expressed in breast cancer cells (BrCCs); however, their genome-wide BrCC functions are unknown. RUNX1 and RUNX2 activate many tumor suppressor pathways in blood and bone lineages, respectively, including attenuation of protein synthesis and cell growth via suppression of ribosomal RNA (rRNA) transcription, which appears contrary to Runx-expression in highly proliferative BrCCs. To define roles for RUNX1 and RUNX2 in BrCC phenotype, we examined the involvement of RUNX1 and RUNX2 in rRNA transcription and generated a genome-wide model for RUNX1 and RUNX2-binding and transcriptional regulation. To validate gene expression patterns identified in our screen, we developed a Real-Time qPCR primer design program, which allows rapid, high-throughput design of primer pairs (FoxPrimer). In BrCCs, RUNX1 and RUNX2 regulate genes that promote invasiveness and do not affect rRNA transcription, protein synthesis, or cell growth. We have characterized in vitro functions of Runx proteins in BrCCs; however, the relationships between Runx expression and diagnostic/prognostic markers of breast cancer (BrCa) in patients are not well studied. Immunohistochemical detection of RUNX1 and RUNX2 in BrCa tissue microarrays reveals RUNX1 expression is associated with early, smaller tumors that are ER+ (estrogen receptor), HER2+, p53-, and correlated with androgen receptor (AR) expression; RUNX2 expression is associated with late-stage, larger tumors that are HER2+. These results show that the functions and expression patterns of NM-associated RUNX1 and RUNX2 are context-sensitive, which suggests potential disease-specific roles. Two functionally disparate genomic sequence types bind to the NM: matrix associated regions (MARs) are functionally associated with transcriptional repression and scaffold associated regions (SARs) are functionally associated with actively expressed genes. It is unknown whether malignant nuclear disorganization affects the functions of MARs/SARs in BrCC. We have refined a method to isolate nuclear matrix associated DNA (NM-DNA) from a structurally preserved NM and applied this protocol to normal mammary epithelial cells and BrCCs. To define transcriptional functions for NM-DNA, we developed a computational algorithm (PeaksToGenes), which statistically tests the associations of experimentally-defined NM-DNA regions and ChIP-seq-defined positional enrichment of several histone marks with transcriptome-wide gene expression data. In normal mammary epithelial cells, NM-DNA is enriched in both MARs and SARs, and the positional enrichment patterns of MARs and SARs are strongly associated with gene expression patterns, suggesting functional roles. In contrast, the BrCCs are significantly enriched in the silencing mark H3K27me3, and the NM-DNA is enriched in MARs and depleted of SARs. The MARs/SARs in the BrCCs are only weakly associated with gene expression patterns, suggesting that loss of normal DNA-matrix associations accompanies the disease state. Our results show that structural preservation of the in situ NM allows isolation of both MARs and SARs, and further demonstrate that in a disorganized, cancerous nucleus, normal transcriptional functions of NM-DNA are disrupted. Our studies on nuclear organization in BrCC, show that the disorganized phenotype of the cancer cell nucleus is accompanied by deregulated transcriptional functions of two constituents of the NM. These results reinforce the role of the NM as an important structure-function component of gene expression regulation